Workers in precious metals refineries are at risk of exposure to salt compounds of the platinum group metals through inhalation, as well as through the skin. Rhodium salt permeation through the skin has previously been proven using rhodium trichloride (RhCl3) dissolved in synthetic sweat at a pH of 6.5. However, the skin surface pH of refinery workers may be lower than 6.5. The aim of this study was to investigate the influence of pH 6.5 and 4.5 on the in vitro permeation of rhodium through intact Caucasian skin using Franz diffusion cells. A concentration of 0.3 mg mL–1 rhodium was used and analyses were performed using inductively coupled plasma mass spectrometry and inductively coupled plasma optical emission spectrometry. Results indicated a cumulative increase in permeation over 24 h. Rhodium permeation after 12 h was significantly greater at pH 4.5 (1.56 ± 0.24 ng cm–2) than at 6.5 (0.85 ± 0.13 ng cm–2; p = 0.02). At both pH levels, there was a highly significant difference (p < 0.01) between the mass of rhodium remaining in the skin (1428.68 ± 224.67 ng cm–2 at pH 4.5 and 1029.90 ± 115.96 ng cm–2 at pH 6.5) and the mass that diffused through (0.88 ± 0.17 ng cm–2 at pH 4.5 and 0.62 ± 0.10 ng cm–2 at pH 6.5). From these findings, it is evident that an acidic working environment or low skin surface pH may enhance permeation of rhodium salts, contributing to sensitization and adverse health effects.
A novel composite material has been developed from natural rubber and leather waste, and a corresponding patent has been filed. This new material may be incorporated into textile and footwear products. However, as leather waste contains chromium, the biocompatibility of this new material and its safety for use in humans must be investigated. The aim of the present study was to investigate the presence of chromium in this new material, determine the amount of each form of chromium present (trivalent or hexavalent), and evaluate the potential cytotoxic and genotoxic effects of the novel composite in two cell lines. The cellular viability was quantified using the MTT3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction method and neutral red uptake assay, and genotoxic damage was analyzed using the comet assay. Our findings indicated that the extracts obtained from the composite were severely cytotoxic to both cell lines tested, and additionally highly genotoxic to MRC-5 cells. These biological responses do not appear to be attributable to the presence of chromium, as the trivalent form was predominantly found to be present in the extracts, indicating that hexavalent chromium is not formed during the production of the novel composite. The incorporation of this new material in applications that do not involve direct contact with the human skin is thus indicated, and it is suggested that the chain of production of this material be studied in order to improve its biocompatibility so that it may safely be used in the textile and footwear industries.
The aim of the present study was to compare a group of workers with stable lead levels with a group of workers with fluctuating lead levels in terms of selected hematological, biochemical, and immunological parameters. The examined group included male workers occupationally exposed to lead. Blood lead (PbB) levels were measured every 3 months during the 5-year observation. Based on standard deviation of mean PbB levels, the examined population was divided into two groups: low level of fluctuation (L-SD) and high level of fluctuation (H-SD) groups. The mean and maximal PbB levels were significantly higher in the H-SD group than in the L-SD group by 9 and 22%, respectively. At the same time, the maximal level of zinc protoporphyrin (ZPP) and standard deviation of mean ZPP level were higher in the H-SD group by 29 and 55%, respectively. The maximal level of hemoglobin and white blood cell (WBC) count as well as standard deviation of the mean hemoglobin level and WBC count were higher in the H-SD group by 2, 8, 58, and 24%, respectively. The expression of nuclear factor kappa-B1 gene and telomerase reverse transcriptase gene was significantly greater in the H-SD group than in the L-SD group by 11 and 28%, respectively. Workers occupationally exposed to lead do not represent a homogenous population. Some present stable lead levels, whereas others have fluctuating lead levels. These fluctuations are related to secondary changes in ZPP and hemoglobin levels as well as WBC count.
The present study was designed to investigate the neuroprotective effect of hesperetin (Hp) against cadmium (Cd)-induced neurotoxicity in rats. Cadmium (3 mg/kg body weight (b.w.), subcutaneous) administration for 3 weeks demonstrated neurotoxicity in rats by the decreased activity of acetylcholinesterase in the brain. The oxidative stress markers (thiobarbituric acid reactive substances and protein carbonyls) were significantly increased with decreased enzymatic (superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase) and non-enzymatic antioxidants (reduced glutathione, total sulphydryl groups and vitamin C). The proteolytic and membrane-bound enzymes (Na+ K+-ATPase, Mg2+-ATPase and Ca2+-ATPase) were also decreased with increased apoptotic markers (Bcl2 Associated X Protein (Bax), cytochrome C, caspase 3 and 9) and decreased anti-apoptotic marker (B-cell lymphoma 2 (Bcl2)) in the brain of Cd-treated rats. Moreover, Cd administration significantly decreased the mitochondrial electron transport chain complexes (I, II, III and IV) in the brain of rats. Preadministration of Hp (40 mg/kg b.w., oral) significantly attenuated the Cd-induced oxidative stress and mitochondrial dysfunction, restored the antioxidant and membrane-bound enzyme activities and decreased apoptosis in the brain of rats.
The aim of this study was to evaluate the genotoxicity of the herbicide diuron in the wing-spot test and a novel wing imaginal disk comet assay in Drosophila melanogaster. The wing-spot test was performed with standard (ST) and high-bioactivation (HB) crosses after providing chronic 48 h treatment to third instar larvae. A positive dose–response effect was observed in both crosses, but statistically reduced spot frequencies were registered for the HB cross compared with the ST. This latter finding suggests that metabolism differences play an important role in the genotoxic effect of diuron. To verify diuron’s ability to produce DNA damage, a wing imaginal disk comet assay was performed after providing 24 h diuron treatment to ST and HB third instar larvae. DNA damage induced by the herbicide had a significantly positive dose–response effect even at very low concentrations in both strains. However, as noted for the wing-spot test, a significant difference between strains was not observed that could be related to the duration of exposure between both assays. A positive correlation between the comet assay and the wing-spot test was found with regard to diuron genotoxicity.
Recent studies have indicated an increased incidence of toxic neuropathies among waste management workers (WMW) possibly linked to increased detection of heavy metals in municipal solid wastes. The present study evaluated serum levels of some heavy and essential trace metals in relation to oxidant/antioxidant status of WMW. One hundred and twenty-six WMW and 84 non-WMW (control) were recruited. Metal/element concentration was measured by atomic absorption spectrophotometry and oxidant/antioxidant markers were determined using standard procedures. The WMW exhibited significantly (p < 0.001) decreased ferric reducing ability of plasma (FRAP) and higher levels of ceruloplasmin (Cp) and malondialdehyde. Iron (Fe) and copper (Cu) levels were significantly lower (p < 0.05) and higher (p < 0.001), respectively in WMW when compared with control while levels of other trace elements were not significantly different between these groups. Lead (Pb) and chromium levels were significantly higher (p < 0.001 and p < 0.05, respectively) in WMW while mercury levels were comparable with those of control subjects. In WMW, Cp (r = –0.182; p > 0.05) and FRAP (r = 0.277; p < 0.05) negatively and positively correlated with Pb, respectively, while a positive correlation was observed between zinc (r = 0.230; p < 0.05) and Pb and between Cu (r = 0.541; p > 0.001) and Fe. Overall, the decreased antioxidant capacity and increased oxidative stress observed in WMW in this study may be related to their blood levels of heavy and essential trace metals. Conscious efforts are required, therefore, to reduce risk and protect WMW from toxic neuropathies and other adverse health consequences of occupational exposure.
Even though there are contradictory reports regarding the cellular and molecular changes induced by mobile phone emitted radiofrequency radiation (RFR), the possibility of any biological effect cannot be ruled out. In view of a widespread and extensive use of mobile phones, this study evaluates alterations in male germ cell transformation kinetics following RFR exposure and after recovery. Swiss albino mice were exposed to RFR (900 MHz) for 4 h and 8 h duration per day for 35 days. One group of animals was terminated after the exposure period, while others were kept for an additional 35 days post-exposure. RFR exposure caused depolarization of mitochondrial membranes resulting in destabilized cellular redox homeostasis. Statistically significant increases in the damage index in germ cells and sperm head defects were noted in RFR-exposed animals. Flow cytometric estimation of germ cell subtypes in mice testis revealed 2.5-fold increases in spermatogonial populations with significant decreases in spermatids. Almost fourfold reduction in spermatogonia to spermatid turnover (1C:2C) and three times reduction in primary spermatocyte to spermatid turnover (1C:4C) was found indicating arrest in the premeiotic stage of spermatogenesis, which resulted in loss of post-meiotic germ cells apparent from testis histology and low sperm count in RFR-exposed animals. Histological alterations such as sloughing of immature germ cells into the seminiferous tubule lumen, epithelium depletion and maturation arrest were also observed. However, all these changes showed recovery to varied degrees following the post-exposure period indicating that the adverse effects of RFR on mice germ cells are detrimental but reversible. To conclude, RFR exposure-induced oxidative stress causes DNA damage in germ cells, which alters cell cycle progression leading to low sperm count in mice.
Lead is a toxic heavy metal, and prevention of human exposure to lead has not been accomplished yet. The toxicity of lead is continually being investigated, and the molecular mechanisms of its toxicity are still being revealed. In this study, we used a novel method to examine thiol (SH)/disulfide homeostasis in workers who were occupationally exposed to lead. A total of 80 such workers and 70 control subjects were evaluated, and their native and total SH values were measured in serum using a novel method; their blood lead levels were also assessed. The novel method used for SH measurements was based on the principle of measuring native SH, after which disulfide bonds were reduced and total SHs were measured. These measurements allowed us to calculate disulfide amounts, disulfide/total SH percent ratios, disulfide/native SH percent ratios, and native SH /total SH percent ratios. We found that disulfide levels were significantly higher in workers who were exposed to lead (21.08(11.1–53.6) vs. 17.9(1.7–25), p < 0.001). Additionally, the disulfide/native SH and disulfide/total SH percent ratios were higher in exposed workers, while the native SH/total SH percent ratios were higher in the control subjects. Furthermore, the lead and disulfide levels showed a positive correlation, with p < 0.001 and a correlation coefficient of 0.378. Finally, the novel method used in this study successfully showed a switch from SH to disulfide after lead exposure, and the method is fully automated, easy, cheap, reliable, and reproducible. Use of this method in future cases may provide valuable insights into the management of lead exposure.
Zinc (Zn) is known to interact with lead (Pb) and cadmium (Cd) reversing their toxicity and reducing their concentrations. However, lactating women are at high risk of developing Zn deficiency, which may result in Pb and Cd intoxication or increased exposure of breast-fed infants to Pb and Cd from breast milk. The aim of this study was to determine Zn, Pb, and Cd concentrations and examine their relationship in serum and breast milk of lactating women in Ibadan, Nigeria. Ninety-two lactating women were recruited into this study. Anthropometric measurements were assessed by standard methods while serum and breast milk concentrations of Zn, Pb, and Cd were assessed by atomic absorption spectrophotometry. Data analyzed statistically by Student’s t test, Pearson’s correlation coefficient, and a multiple regression model were significant at p < 0.05. Zn deficiency was observed in 12 (17.1%) of lactating women. Breast milk levels of Zn, Pb, and Cd were significantly higher than their levels in serum, whereas the ratios Zn:Pb and Zn:Cd in milk were significantly less than serum ratios. Significant negative correlation was observed between milk Pb and serum Zn:Pb while milk Cd correlated positively with milk Zn. Significant positive correlations were observed between serum Zn and serum Zn:Pb, serum Zn and serum Zn:Cd, as well as serum Zn:Cd and serum Zn:Pb. Serum Cd and serum Zn were significantly negatively related. Significant negative correlations between serum Pb and serum Zn:Pb as well as milk Zn:Pb. Serum Cd and serum Zn:Pb as well as serum Zn:Cd correlated negatively. Milk Cd and Zn/Cd positively related with milk Pb while milk Zn was a negatively related with milk Pb in a multiple regression model (R 2 = 0.333; p = 0.023). Breast milk may be contaminated by toxic metals. However, Zn supplementation in deficient mothers may protect maternal and infant health.
The health effects of bisphenol A (BPA) have become a great concern in recent years. In this study, the reproductive toxicity of BPA was investigated. Male CD-1 mice were orally administrated with BPA (0, 100, 300 and 600 mg kg–1 body weight) for 56 consecutive days. Results showed that relative testis weight to total body weight was significantly lower in the high-dose group (p < 0.01, p < 0.05). Microscopic examination under light and transmission electron microscopes showed disorders of spermatogenesis after BPA exposure, including rough basal lamina of seminiferous tubules and damage of tight junctions between Sertoli cells. Further study by terminal-deoxynucleoitidyl transferase–mediated nick end labelling assay showed a significant induction of apoptosis in the testis tissue of the BPA groups (p < 0.01). Immunohistochemical study found that the expression of androgen-binding protein (ABP) was significantly decreased in BPA-treated mice (p < 0.01). Our results indicated that impairment of the basal lamina of seminiferous tubules and tight junctions may contribute to BPA-induced cell injury. A decrease in the level of ABP could be the possible mechanism for the reproductive toxicity of BPA. These findings provided direct evidence and novel insight into the reproductive toxicity of BPA and may have implications for understanding the toxicity of other endocrine disruptors.
Carbon monoxide (CO) is a colourless and odourless gas appearing as a result of incomplete combustion of carbon-containing fuels. Many domestic or occupational poisonings are caused by CO exposure. Malfunctioning heating systems, improperly ventilated motor vehicles, generators, grills, stoves and residential fires may be listed in the common sources of CO exposure. The aim of this study was to emphasize the significance of early diagnosis of CO poisoning with non-invasive measurement of CO levels of the patients with non-specific symptoms using a pulse oximeter device in the triage. Our study was a cross-sectional study. Patients who presented to the emergency department (ED) due to non-specific symptoms and had a Canadian Triage and Acuity scale level of 4 or 5 were included in the study; 106 (5.9%) of 1788 patients admitted during the study period were diagnosed with CO poisoning. Patients with CO poisoning and the other patients had statistically significant differences in terms of presenting symptoms, namely, headache, dizziness, nausea, and vomiting. More CO poisoning cases were admitted in the fall and winter compared to the spring and summer. The number of CO poisoning victims can be decreased if preventive measures like CO monitoring systems and well-designed ventilation systems are generalized at homes and workplaces. Measurement of carboxyhaemoglobin levels of patients presenting to ED due to non-specific symptoms like headache and dizziness during cold seasons and winter months using a pulse CO-oximeter should be a part of the routine of emergency medicine triage.
Currently, in India, air pollution is widespread in urban areas where vehicles are major contributors. The aim of this study was to investigate the level of exposure in traffic police officers exposed to vehicle exhaust for less than 8 h/day. The specific objective of the study was to determine the levels of carboxyhaemoglobin (COHb) in these officers. The effect of exposure for 8 h/day is known, but shorter durations of chronic exposure need to be investigated, and there is a need to explore the policy options in this exposed population. This cross-sectional study, included non-smoking traffic police officers between 30 and 50 years of age working for more than 2 years in busy traffic junctions. The cases were sex matched with controls of same age group, working in offices at a teaching hospital. Venous blood was collected at the end of 3 h of duty for estimation of COHb among both the groups. The COHb levels were expressed as percentage values. Differences between the COHb levels among the traffic police officers and office workers were analysed using the Mann-Whitney U test and considered significant at p < 0.05. Traffic police officers had significantly elevated COHb levels compared with the controls; 76.5% of traffic police officers had COHb >2.5% compared with no office workers at this level and 41.2% of the police officers had COHb levels >4%. Overall, 53.8% of officers with COHb >2.5% reported headaches compared with 15.8% of officers with COHb <2.5%.
The purpose of this study is the evaluation of possible toxicological effects on dental personnel, who are exposed to the production materials of prostheses during their entire working life. In this study, the level of methyl methacrylate (MMA) in ambient air was measured as an indicator of external exposure on the personnel. In order to evaluate the possible toxic effects of oxidative stress, which is thought to play an important role in the formation process of many diseases such as cancer, blood samples of volunteers were examined via the ultraviolet-spectroscopic determination of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase antioxidant enzyme activities, comparing occupationally MMA-exposed (n = 69) and control (n = 67) groups. In these groups, malondialdehyde (MDA) and glutathione levels were also determined by the same method. The results showed that SOD activity and MDA and glutathione levels were significantly higher in the exposed group when compared with the control group (p < 0.001). A significant decrease was determined in the glutathione peroxidase activities of the exposed group (p < 0.05). No significant difference in CAT activities between the groups has been found. When the results obtained in the study are considered, it is suggested that an adaptive response might be developed by dental technicians against low-level MMA exposure.
This cross-sectional study examined whether people who are exposed to mercury (Hg) vapours in ongoing artisanal gold mining activities have alteration in kidney function monitoring parameters. The study enrolled 164 miners and 127 participant controls. The Hg concentrations for miners and control participants were measured in blood (B-Hg; median 7.0 vs. 2.5 µg/L), urine (U-Hg; median 3.9 vs. 1.5 µg/g creatinine) and hair (H-Hg; median 0.8 vs. 0.4 µg/g hair). The biomarkers of renal function were creatinine, albumin and excretion of β-2 microglobulin. Glomerular filtration rate (eGFR) was calculated using the chronic kidney disease epidemiology collaboration equation. Significant statistical differences were found in Hg concentrations and eGFR levels between the two study groups (p < 0.01) but not with the other biomarkers of renal function. A multiple regression model was applied to explore the relationship of eGFR levels and Hg concentrations. However, no association was found between the prevalence of reduced eGFR (<71.96 mL/min/1.73 m2) and the B-Hg or U-Hg levels after adjustment for covariates. Nevertheless, it was observed that having B-Hg levels above 10 µg Hg/L decreased the eGFR by 1.7 mL/min/1.73 m2 (confidence interval 95% –5.1 to 1.7) compared to having levels below 2.0 µg Hg/L. Our results found no support for kidney damage associated with Hg vapour exposure in ongoing artisanal gold mining, whose population has a level of Hg exposure from low to moderate (B-Hg from 3.4 to 11.0 µg/L and U-Hg from 1.3 to 9.6 µg/g creatinine).
This study evaluated the effects of three vehicles—ethanol (EtOH), isopropyl alcohol (IPA), and isopropyl myristate (IPM)—on stratum corneum (SC) absorption and diffusion of the [14C]-model compounds benzoic acid and butenafine hydrochloride to better understand the transport pathways of chemicals passing through and resident in SC. Following application of topical formulations to human dermatomed skin for 30 min, penetration flux was observed for 24 h post dosing, using an in vitro flow-through skin diffusion system. Skin absorption and penetration was compared to the chemical-SC (intact, delipidized, or SC lipid film) binding levels. A significant vehicle effect was observed for chemical skin penetration and SC absorption. IPA resulted in the greatest levels of intact SC/SC lipid absorption, skin penetration, and total skin absorption/penetration of benzoic acid, followed by IPM and EtOH, respectively. For intact SC absorption and total skin absorption/penetration of butenafine, the vehicle that demonstrated the highest level of sorption/penetration was EtOH, followed by IPA and IPM, respectively. The percent doses of butenafine that were absorbed in SC lipid film and penetrated through skin in 24 h were greatest for IPA, followed by EtOH and IPM, respectively. The vehicle effect was consistent between intact SC absorption and total chemical skin absorption and penetration, as well as SC lipid absorption and chemical penetration through skin, suggesting intercellular transport as a main pathway of skin penetration for model chemicals. These results suggest the potential to predict vehicle effects on skin permeability with simple SC absorption assays. As decontamination was applied 30 min after chemical exposure, significant vehicle effects on chemical SC partitioning and percutaneous penetration also suggest that skin decontamination efficiency is vehicle dependent, and an effective decontamination method should act on chemical solutes in the lipid domain.
Fluazifop-p-butyl (FPB) is a selective aryloxyphenoxypropionate herbicide. Its phytotoxicity mechanism involves inhibition of lipid biosynthesis, free-radical generation, and oxidative stress in vulnerable plants. This study evaluates the impact of orally administered FPB on selected tissues in non-target animal model. Twenty-four male wistar rats (160–180g) were randomized into groups (I–IV). Group-I served as control, while animals in groups II, III, and IV received FPB at 18.75, 37.5, and 75 mg/kg body weight/day p.o., respectively, for 21 days. FPB caused significant (p < 0.05) increase in plasma biomarkers of renal and hepatic function (urea, creatinine, bilirubin, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase) when compared to control. Significant reductions in testicular ascorbic acid, glutathione, and activities of glutathione-S transferase, superoxide dismutase, and catalase were observed in FPB-treated animals when compared to control, in a dose-dependent manner. This was accompanied by increased testicular lipid peroxidation in the treated groups. Furthermore, a significant decrease in testicular acid phosphatase and -glutamyl transferase activities was also observed in the FPB-treated groups in a dose-dependent manner compared to control. However, testicular lactate dehydrogenase activity was significantly increased in the FPB-treated rats when compared to control. Additionally, histopathological studies revealed severe interstitial oedema and congestion of testicular blood vessels in the FPB-treated groups. Overall, data from this study suggest that FPB induced hepatotoxicity, nephrotoxicity, and oxidative stress-mediated alteration of testicular functions in rat.
Metalworking fluids (MWFs) are complex formulations designed for effective lubricating, cooling, and cleaning tools and parts during machining operations. Adverse health effects such as respiratory symptoms, dermatitis, and cancer have been reported in workers exposed to MWFs. Several constituents of MWFs have been implicated in toxicity and have been removed from the formulations over the years. However, animal studies with newer MWFs demonstrate that they continue to pose a health risk. This investigation examines the hypothesis that unrecognized health hazards exist in currently marketed MWF formulations that are presumed to be safe based on hazard assessments of individual ingredients. In vivo 13-week inhalation studies were designed to characterize and compare the potential toxicity of four MWFs: Trim VX, Cimstar 3800, Trim SC210, and Syntilo 1023. Male and female Wistar Han rats or Fischer 344N/Tac rats and B6C3F1/N mice were exposed to MWFs via whole-body inhalation at concentrations of 0, 25, 50, 100, 200, or 400 mg/m3 for 13 weeks, after which, survival, body and organ weights, hematology and clinical chemistry, histopathology, and genotoxicity were assessed following exposure. Although high concentrations were used, survival was not affected and toxicity was primarily within the respiratory tract of male and female rats and mice. Minor variances in toxicity were attributed to differences among species as well as in the chemical components of each MWF. Pulmonary fibrosis was present only in rats and mice exposed to Trim VX. These data confirm that newer MWFs have the potential to cause respiratory toxicity in workers who are repeatedly exposed via inhalation.
Heavy metal determination in ambient air is an important task for environmental researchers because of their toxicity to human beings. Some heavy metals (hexavalent chromium (Cr), arsenic (As), cadmium (Cd) and nickel (Ni)) have been listed as carcinogens. Furthermore, heavy metals in the atmosphere can accumulate in various plants and animals and enter humans through the food chain. This article reviews the determination of heavy metals in the atmosphere in different areas of the world since 2006. The results showed that most researchers concentrated on toxic metals, such as Cr, Cd, Ni, As and lead. A few studies used plant materials as bio-monitors for the atmospheric levels of heavy metals. Some researchers found higher concentrations of heavy metals surrounding industrial areas compared with residential and/or commercial areas. Most studies reported the major sources of the particulate matter and heavy metals in the atmosphere to be industrial emissions, vehicular emissions and secondary aerosols.
There is currently no consensus on the best exposure metric(s) for expressing nanoparticle (NP) dose. Although surface area has been extensively studied for inflammatory responses, it has not been as thoroughly validated for cytotoxicity or oxidative stress effects. Since inhaled NPs deposit and interact with lung cells based on agglomerate size, we hypothesize that mass concentration combined with aerosol size distribution is suitable for NP risk assessment. The objective of this study was to evaluate different exposure metrics for inhaled 5 nm titanium dioxide aerosols composed of small (SA < 100 nm) or large (LA > 100 nm) agglomerates at 2, 7, and 20 mg/m3 on rat lung inflammatory, cytotoxicity, and oxidative stress responses. We found a significant positive correlation (r = 0.98, p < 0.01) with the inflammatory reaction, measured by the number of neutrophils and the mass concentration when considering all six (SA + LA) aerosols. This correlation was similar (r = 0.87) for total surface area. Regarding cytotoxicity and oxidative stress responses, measured by lactate dehydrogenase and 8-isoprostane, respectively, and mass or total surface area as an exposure metric, we observed significant positive correlations only with SA aerosols for both the mass concentration and size distribution (r > 0.91, p < 0.01), as well as for the total surface area (r > 0.97, p < 0.01). These data show that mass or total surface area concentrations alone are insufficient to adequately predict oxidant and cytotoxic pulmonary effects. Overall, our study indicates that considering NP size distribution along with mass or total surface area concentrations contributes to a more mechanistic discrimination of pulmonary responses to NP exposure.
Lead acts as an antagonist of the N-methyl-
The aim of this study was to evaluate neurobehavioral toxicity of single-walled (SWNTs) and multiwalled carbon nanotubes (MWNTs) in mice.
Male NMRI mice were randomized into 5 groups (n = 10 each): Normal control (NC) group was injected intraperitoneally (i.p.) with phosphate-buffered saline (PBS) solution (pH 7.8; ca. 1 mL), MW80 and MW800 groups were injected with either i.p. 80 or 800 mg kg–1 MWNTs suspended in 1 mL of PBS and SW80 and SW800 groups were injected with either i.p. 80 or 800 mg kg–1 SWNTs suspended in 1 mL of PBS. After 2 weeks, five mice from each group were evaluated for brain-derived neurotrophic factor (BDNF) messenger RNA expression and protein content of brain tissues. Locomotion, anxiety, learning and memory, and depression were measured by open field test (OFT), elevated plus-maze (EPM), object recognition test (ORT), and forced swimming test (FST), respectively.
Ambulation time and center arena time in the OFT did not change among groups. In the EPM paradigm, SWNTs (800 mg kg–1) and MWNTs (80 and 800 mg kg–1) showed an anxiogenic effect. In ORT, MWNTs (80 mg kg–1) increased the discrimination ratio while in FST, MWNTs showed a depressant effect as compared to vehicle. The BDNF gene expression in mice treated with 80 and 800 mg kg–1 SWNTs or 80 mg kg–1 MWNTs decreased as compared to NC mice although BDNF gene expression increased in mice that were treated with 800 mg kg–1 MWNTs. The whole brain BDNF protein content did not change among groups.
Our study showed that i.p. exposure to carbon nanotubes (CNTs) may result in behavioral toxicity linked with expression of depression or anxiety that depends on the type of CNTs. In addition, exposure to CNTs changed BDNF gene expression.
Methyl isocyanate (MIC) is a toxic industrial chemical that is documented as a potent respiratory toxicant. We investigated cell-mediated immunity (CMI) in the MIC-exposed long-term survivors and their offspring born after the Bhopal gas-leak tragedy in 1984. Several earlier reports show inconsistency in the assessment of immunological effects of MIC on the human population. In these studies, important factors including lifestyle attributes were overlooked. We incorporated these factors also in our study of the basic cell-mediated immune function in the Bhopal MIC-affected population. Twenty-seven years after exposure, we assessed the circulating T-lymphocyte frequency using E-Rosette assay. A total of 46 MIC-exposed healthy long-term survivors and their offspring were studied vis-a-vis parallel gender–age group-matched unexposed controls from Bhopal and various other regions of India. The influence of several lifestyle variabilities (smoking, alcohol intake, and tobacco chewing) on T-lymphocyte frequency was also taken into consideration. Our observations suggest that Erythrocyte-Rosette-forming cell (E-RFC) distribution frequency is largely insignificant in the MIC-affected population as compared to controls (p > 0.05). In the MIC-affected tobacco chewers, there was a trend of suppression in CMI (relative decrease = 10.3%) as compared to nonchewers. Overall, our results show negligible long-term effect of MIC on CMI measured in terms of E-RFC frequency. These observations are not in agreement with earlier findings that immunosuppressive effects of MIC exposure persist in the T-cells of the affected population. However, atypical lymphocytes were frequently observed as E-RFC in the exposed females when compared to all other subgroups. Hematopoietic disorders (atypical lymphocytosis) in the MIC-affected population along with previous reports on the cytogenetic and humoral immune system linking cancer risk and chronic obstructive pulmonary disease (COPD) are important.
The objective of the present study was to systematically determine the effects of 50 Hertz (Hz) magnetic fields (MFs) on biochemical parameters in rats. Sixty-four adult (5 weeks old, 140–165 g) male Sprague–Dawley rats were randomly divided into four groups: sham, 20 µTesla (µT), 100 µT, and 500 µT 50 Hz MF (n = 16 in each group). The rats in the MF groups were exposed for 2 h daily for up to 4 weeks. Under these experimental conditions, body weight, organ coefficients, biochemical parameters (blood lipids, myocardial enzymes, liver function, and renal function) were measured. We found that 50 Hz MFs had no significant effects on growth or on the majority of blood biochemical parameters, with the exception of creatinine and cholesterol. However, the changes in creatinine and cholesterol were relatively small and unlikely to be clinically relevant.
The potential protective effect of citicoline on aluminum chloride-induced cognitive deficits was investigated in rats. In a Morris water maze, administration of aluminum chloride to rats for 90 days resulted in increased escape latency to reach the platform and decreased swimming speed in acquisition trials. Similarly, in probe trials, the time required to reach the hidden platform was increased and the time spent in the target quadrant was reduced. Also, administration of aluminum chloride to rats for 90 days increased the reference and working memory errors and time required to end the task in the radial arm maze. In addition, this treatment decreased the step-through latency in the passive avoidance test. Concurrently, treatment of rats with aluminum chloride for 90 days increased hippocampal glutamate, malondialdehyde, and nitrite levels and decreased intracellular reduced glutathione level. In the citicoline-treated group, aluminum chloride-induced learning and memory impairments as assessed by the Morris water maze, radial arm maze, and passive avoidance tests were inhibited. At the same time, treatment of rats with citicoline prevented the biochemical alterations induced by aluminum chloride in the hippocampus. It can be concluded that elevation of hippocampal glutamate level with consequent oxidative stress and nitric oxide (NO) overproduction may play an important role in aluminum-induced cognitive impairments. Also, our results suggest, for the first time, that citicoline can protect against the development of these cognitive deficits through inhibition of aluminum-induced elevation of glutamate level, oxidative stress, and NO overproduction in the hippocampus.
The aim of this study was to investigate the beneficial effects of zinc (Zn) in preventing lead (Pb)-induced reproductive toxicity in Wistar rats. The rats were divided into four groups, namely, control group, Pb group, Zn group, and Pb + Zn group. Animals were exposed to Pb (819 mg of Pb/L) or Zn (71 mg of Zn/L) or both through drinking water for 65 days. Rats exposed to Pb showed decreased weights of testes and accessory sex organs. Significant decrease in the testicular daily sperm production, epididymal sperm count, motility, viability, and number of hypoosmotic tail coiled sperm was observed in Pb-exposed rats. Testicular 3β- and 17β-hydroxysteroid dehydrogenase activity levels and circulatory testosterone levels were also decreased significantly in Pb-exposed rats. A significant increase in the lipid peroxidation products with a significant decrease in the activities of catalase and superoxide dismutase were observed in the testes and epididymis of Pb-exposed rats. Moreover, the testicular architecture showed lumens devoid of sperm in Pb-exposed rats. Supplementation of Zn mitigated Pb-induced oxidative stress and restored the spermatogenesis and steroidogenesis in Pb-exposed rats. In conclusion, cotreatment of Zn is effective for recovering suppressed spermatogenesis, steroidogenesis, elevated oxidative status, and histological damage in the testis of rats treated with Pb.
Pesticides are one of the most potentially harmful chemicals introduced into the environment, and their adverse impacts on non-target organisms can be significant. The present study was conducted to shed light on effects of locally used insecticides chlorpyrifos (CPF) and lambda cyhalothrin (LCT) on oxidative stress biomarkers in human erythrocytes. The activity of catalase (CAT), superoxide dismutase (SOD), and protein contents as well as the levels of malondialdehyde (MDA) and osmotic fragility (OF) were measured in human erythrocytes exposed to CPF at concentrations of 0, 100, 500, 1000, and 2000 ppm and LCT at concentrations of 0, 100, 300, 600, and 800 ppm for 1 h and 3 h at 37°C. MDA levels and OF of erythrocytes were significantly higher in erythrocytes incubated with CPF and LCT at increasing concentrations of both insecticides and increased incubation time. However, erythrocyte CAT and SOD activities were decreased at all concentrations of CPF and LCT tested. Protein oxidation products were decreased at lower doses of CPF (100 and 500 ppm); at higher doses (1000 and 2000 ppm), total protein content was increased compared with control. In contrast LCT was associated with decreased in protein contents at all the concentrations. These results clearly demonstrated that CPF and LCT can induce oxidative stress in human erythrocytes (in vitro).
Polybrominated diphenyl ethers (PBDEs) exist extensively in the environment as contaminants, in which 2,2',3,3',4,4',5,5',6,6'-decabrominated diphenyl ether (BDE-209) is the most abundant PBDE found in human samples. BDE-209 has been shown to cause neurotoxicity of primary sensory neurons with few effective therapeutic options available. Here, cultured dorsal root ganglion (DRG) neurons were used to determine the therapeutic effects of insulin-like growth factor-1 (IGF-1) on BDE-209-induced neurotoxicity. The results showed that IGF-1 promoted neurite outgrowth and cell viability of DRG neurons with BDE-209-induced neurotoxicity. IGF-1 inhibited oxidative stress and apoptotic cell death caused by BDE-209 exposure. IGF-1 could reverse the decrease in growth-associated protein-43 (GAP-43) and calcitonin gene-related peptide (CGRP), but not neurofilament-200 (NF-200), expression resulting from BDE-209 exposure. The effects of IGF-1 could be blocked by the extracellular signal-regulated protein kinase (ERK1/2) inhibitor PD98059 and the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, either alone or in combination. IGF-1 may play an important role in neuroprotective effects on DRG neurons with BDE-209-induced neurotoxicity through inhibiting oxidative stress and apoptosis and regulating GAP-43 and CGRP expression of DRG neurons. Both ERK1/2 and PI3K/Akt signaling pathways were involved in the effects of IGF-1. Thus, IGF-1 might be one of the therapeutic agents on BDE-209-induced neurotoxicity.
Diabetes mellitus (DM) is a group of metabolic diseases that may originate from an interaction between genetic and lifestyle risk factors. However, the possible role of occupational chemical exposures in the disease development and progression remains unclear. Therefore, this review aimed to provide a comprehensive evaluation of the relationship between occupational exposure to specific chemical substances or industrial activities and DM morbidity and mortality outcomes. Although some positive findings may support the diabetogenic role of certain pesticides and dioxins in different workplaces, the variable conditions of exposure, the lack of quantitative environmental or biological monitoring data and the different outcomes evaluated do not allow defining a specific exposure-disease causality. Therefore, further epidemiological studies will be necessary to adequately assess modes of action for different substances, dose–response relationships as well as individual susceptibility factors potentially affecting the exposure-disease continuum. Overall, this appears important to adequately assess, communicate and manage risks in occupational chemical exposure settings with the aim to protect workers and build healthier job conditions for diabetic employees.
Lambda cyhalothrin (LCT), a broad-spectrum type II (α-cyano) synthetic pyrethroid pesticide, is widely employed in various agricultural and animal husbandry practices for the control of pests. Acute and chronic exposure to LCT can elicit several adverse effects including oxidative stress. With the objective to investigate nephrotoxicity and neurotoxicity of LCT in mice, we evaluated oxidative stress parameters and histological changes in the kidney and brain of LCT exposed mice. Swiss albino mice were divided randomly into four groups (n = 6 per group) as: (A) corn oil/vehicle control; (B) 0.5 mg/kg body weight (b.w.) LCT; (C) 1 mg/kg b.w. LCT; (D) 2 mg/kg b.w. LCT. Mice were treated orally for 28 days. LCT exposure significantly increased serum urea nitrogen, creatinine and urea levels. LCT exposure also increased lipid peroxidation, superoxide anion generation, nitrite level and decreased the level of reduced glutathione. The activities of superoxide dismutase, catalase and glutathione-S-transferase were depleted significantly in both kidney and brain. Histological examination revealed marked histopathological changes in the kidney and brain of mice that were more pronounced at high dose of LCT. Thus, results of the present study indicate that 28 days oral exposure of LCT causes oxidative damage to the kidney and brain of mice which in turn could be responsible for nephrotoxicity and neurotoxicity. Nevertheless, further detailed studies are required to prove these effects especially after long-term exposure.
Proposition 2, which requires that egg-laying hens be confined only in ways that allow these animals to lie down, stand up, fully extend their limbs and turn around freely, was passed by the voters of California in 2008. These new housing requirements were introduced in the USA and European Union without considering the potential impact of changes in layer hen housing on the health of poultry workers in the new facilities. Particles were collected from ambient air inside a large layer hen complex featuring separate barns with conventional battery caging, enriched caging, or ‘free range’ (aviary) housing during winter, spring, and summer seasons over one year. Toxicity of the particles was evaluated by analysis of inflammatory cell influx into lung lavage fluid after intratracheal instillation into mice. Capacity of the particles to elicit oxidative stress was evaluated using a macrophage cell line engineered with a reporter gene sensitive to nuclear factor B activation. We observed similar pro-inflammatory and pro-oxidant effects of the particles collected from different types of barns and over different seasons, suggesting that standard industrial hygiene techniques for evaluating respirable particles in ambient air can adequately monitor worker risk. Based on particle concentrations found in ambient air in the barns, we can rank the facilities for worker exposure to particles as conventional caging (now banned) approximately equal to enriched caging (permitted under Proposition 2). Aviary housing is associated with increased exposure of workers to particulate matter and, therefore, to greater risk of allergic reactions and/or decreased respiratory function.
In the present studies, the in vitro and in vivo efficacies of a novel cyanide countermeasure, dimethyl trisulfide (DMTS), were evaluated. DMTS is a sulfur-based molecule found in garlic, onion, broccoli, and similar plants. DMTS was studied for effectiveness as a sulfur donor-type cyanide countermeasure. The sulfur donor reactivity of DMTS was determined by measuring the rate of the formation of the cyanide metabolite thiocyanate. In experiments carried out in vitro in the presence of the sulfurtransferase rhodanese (Rh) and at the experimental pH of 7.4, DMTS was observed to convert cyanide to thiocyanate with greater than 40 times higher efficacy than does thiosulfate, the sulfur donor component of the US Food and Drug Administration-approved cyanide countermeasure Nithiodote®. In the absence of Rh, DMTS was observed to be almost 80 times more efficient than sodium thiosulfate in vitro. The fact that DMTS converts cyanide to thiocyanate more efficiently than does thiosulfate both with and without Rh makes it a promising sulfur donor-type cyanide antidote (scavenger) with reduced enzyme dependence in vitro. The therapeutic cyanide antidotal efficacies for DMTS versus sodium thiosulfate were measured following intramuscular administration in a mouse model and expressed as antidotal potency ratios (APR = LD50 of cyanide with antidote/LD50 of cyanide without antidote). A dose of 100 mg/kg sodium thiosulfate given intramuscularly showed only slight therapeutic protection (APR = 1.1), whereas the antidotal protection from DMTS given intramuscularly at the same dose was substantial (APR = 3.3). Based on these data, DMTS will be studied further as a promising next-generation countermeasure for cyanide intoxication.
Accidental or intentional releases of toxic gases can have significant public health consequences and emergency resource demands. Management of exposed individuals during hazardous material incidents should be risk and evidence based, but there are knowledge gaps in relation to dermal absorption of gases and management advice for potentially exposed individuals. Using a modified Organization for Economic Co-operation and Development (OECD) in vitro toxicology protocol with human donor skin, this article reports on two common and odorous chemicals, hydrogen sulphide and phosphine. Results show that undamaged human skin provides a good barrier to hydrogen sulphide (up to 800 ppm) and phosphine (up to 1000 ppm) penetration for up to 30 min exposures, with little variability in the presence of clothing or in elevated temperature and humidity conditions. A practical guideline template for skin decontamination has been developed, and implications of the research for first responders are outlined.
Workplace air samples analyzed for benzene at four US refineries from 1976 to 2007 were pooled into a single dataset to characterize similarities and differences between job titles, tasks and refineries, and to provide a robust dataset for exposure reconstruction. Approximately 12,000 non-task (≥180 min) personal samples associated with 50 job titles and 4000 task (<180 min) samples characterizing 24 tasks were evaluated. Personal air sample data from four individual refineries were pooled based on a number of factors including (1) the consistent sampling approach used by refinery industrial hygienists over time, (2) the use of similar exposure controls, (3) the comparability of benzene content of process streams and end products, (4) the ability to assign uniform job titles and task codes across all four refineries, and (5) our analysis of variance (ANOVA) of the distribution of benzene air concentrations for select jobs/tasks across all four refineries. The jobs and tasks most frequently sampled included those with highest potential contact with refinery product streams containing benzene, which reflected the targeted sampling approach utilized by the facility industrial hygienists. Task and non-task data were analyzed to identify and account for significant differences within job-area, task-job, and task-area categories. This analysis demonstrated that in general, areas with benzene containing process streams were associated with greater benzene air concentrations compared to areas with process streams containing little to no benzene. For several job titles and tasks analyzed, there was a statistically significant decrease in benzene air concentration after 1990. This study provides a job and task-focused analysis of occupational exposure to benzene during refinery operations, and it should be useful for reconstructing refinery workers’ exposures to benzene over the past 30 years.
In the present work, we took two nanomaterials (NMs), mesoporous silica nanoparticles (MSNs) and multiwalled carbon nanotubes (MWCNTs), and compared their in vivo toxicity taking albino mice as a test animal model. Presently, conflicting data persist regarding behavior of these NMs with macromolecules like protein and lipid at the cellular level in cell lines as well as in animal models and this generated the interest to study them. The mice were treated orally with a single dose of 50 ppm MWCNTs and intraperitoneally with 10, 25, and 50 mg kg–1 body weight (BW) of MSNs and 1.5, 2.0, and 2.5 mg kg–1 BW of MWCNTs. Liver enzyme markers serum aspartate aminotransferase (AST), alanine aminotransferase, and alkaline phosphatase along with total protein (TP) levels were evaluated 7 days postexposure. No significant differences in organ weight indices or enzyme levels were observed between different treatment doses but there were significant differences between the treatment groups and the controls. Of the three enzymes assayed, AST displayed a peculiar pattern, especially in the MWCNTs intraperitoneally treated group. TP level was significantly increased in the orally treated MWCNTs group. The results showed that MWCNTs even at much smaller doses than MSNs displayed similar toxicity levels, suggesting that toxicity of MWCNTs is greater than MSNs.
Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic derivative of manganese (Mn) and is used as an antiknock agent and octane enhancer in gasoline. In this article, we tested the oxidative stress and heat stress protein (Hsp) 70 levels of gasoline station attendants to explore potential plasma biomarkers. Furthermore, the dose–response relationship was also identified.
A total of 144 workers, including 96 petrol fillers and 48 cashiers, participated in the study. Ambient concentrations of benzene, toluene, ethylbenzene, and xylene (BTEX) and Mn were monitored at nine filling stations. During the measuring process, the individual cumulative exposure index was calculated. Plasma oxidative stress and Hsp70 levels were also analysed using enzyme-linked immunosorbent assay.
The BTEX time-weighted average in office areas was significantly lower than in refuelling areas (p < 0.05). In refuelling areas, the content of Mn ranged from 6.44 μg/m3 to 127.34 μg/m3, which was much higher than that in office areas (3.16–7.22 μg/m3; p < 0.05). Exposed workers had significantly different plasma oxidative stress indicators compared with the control group, respectively: superoxide dismutase (SOD), 39.18 ± 6.05 U/mL versus 52.84 ± 3.87 U/mL; glutathione peroxidase (GSH-Px), 186.07 ± 15.63 U versus 194.38 ± 10.42 U; and malondialdehyde (MDA), 1.68 ± 0.52 nmol/L versus 1.43 ± 0.64 nmol/L (in all comparisons, p < 0.05). Plasma Hsp70 level in the exposed group (2.77 ± 0.64 ng/mL) was significantly higher than in the control group (2.32 ± 0.87 ng/mL; p < 0.05). Furthermore, Hsp70 levels were inversely correlated with the activities of SOD (r = –0.305) and GSH-Px (r = –0.302) in the exposed group (p < 0.05). Moreover, a positive correlation (r = 0.653) was found between plasma Hsp70 levels and plasma MDA levels (p < 0.05).
Exposure to MMT-containing gasoline may result in increasing reactive oxygen stress among filling station attendants. Plasma Hsp70 levels could be used as a sensitive responsive biomarker for exposed workers.
The study was aimed at evaluating the protective role of α-lipoic acid (ALA) on long-term exposure of rats to the combination of chlorpyrifos (CPF) and deltamethrin (DLT). Forty-two (42) male Wistar rats were divided into 6 exposure groups with 7 animals in each group: (I) soya oil (2 ml kg–1), (II) ALA (60 mg kg–1), (III) DLT (6.25 mg kg–1), (IV) CPF (4.75 mg kg–1), (V) (CPF + DLT) DLT (6.25 mg kg–1) and CPF (4.75 mg kg–1; 1/20th of the previously determined median lethal dose) and (VI) (ALA + CPF + DLT) pretreated with ALA (60 mg kg–1) and then co-exposed to CPF and DLT, 45 min later. The regimens were administered by gavage once daily for a period of 16 weeks. Sera obtained from blood collected at the end of the experimental period were used for the evaluation of serum glucose, total protein, albumin, urea, creatinine and the activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase and acetylcholinesterase. The liver homogenate was used to assay for the activities of superoxide dismutase and glutathione peroxidase and the concentrations of malondialdehyde, cytokine and tumour necrotic factor α. The result showed that the combination of CPF and DLT resulted in marked alterations of these biochemical parameters in most cases compared to either of the pesticides singly, supplementation with ALA ameliorated these alterations.
Titanium dioxide nanoparticles (TiO2 NP) are present in several daily use products, and the risks associated with their bioaccumulation must be stablished. Thus, an evaluation of several toxicological-related effects was conducted after intraperitoneal injection of TiO2 NPs in mice. Mice were divided into two groups, which received 2 mg kg–1 day–1 of TiO2 NPs or vehicle saline. Assessments of body and organ weight as well as biochemical, hematological, and histopathological analyses were performed in order to evaluate adverse effects. The results showed that treatment resulted in an increased visceral and abdominal fat deposition, as well as a mononuclear inflammatory infiltrates in the abdominal fat tissue. The TiO2 NPs induced significant decrease in the weight gain and splenomegaly. Additionally, TiO2 NP-treated mice showed altered hematological parameters and significant liver injuries, which were characterized by histopathological and biochemical changes. Our results also indicated that TiO2 NPs were absorbed and significantly accumulated in the spleen, liver, and kidney. These results showed the ability of TiO2 NPs to infiltrate different organs and to induce inflammation and liver and spleen damage with visceral fat accumulation. The data obtained are useful for the governmental authorities to legislate and implement regulations concerning the use and the production of this kind of material that might be hazardous to the living beings, as well as to the environment.
Previous cross-sectional studies have shown that exposure to cleaning chemicals among health-care workers (HCWs) is associated with respiratory disorders and ventilatory function changes. This study aimed to further explore this association using a longitudinal approach. A prospective 2-year follow-up study was carried out at a tertiary care hospital in Saudi Arabia from June 2012 to June 2014 among 56 nurses who were responsible for disinfection and sterilization of medical instruments and equipment. The workplaces of the participants were assessed for engineering, environmental, and safety control measures. Self-administered questionnaires were distributed to all participants to assess their exposure to cleaning chemicals and their medical history. Spirometric parameters were measured for all nurses in 2012 (baseline) and again in 2014 (follow-up). The prevalence of work-related respiratory symptoms did not increase significantly over this time. Among all the spirometric parameters, only forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio decreased significantly, and only 10.7% of participants who were exposed to cleaning chemicals for more than 10 years had FEV1 and FVC less than their longitudinal normal limits at the end of the study. Smoking and gender were associated with statistically significant decreases in some of the spirometric parameters. Our 2-year follow-up study did not demonstrate significant association between exposure to cleaning chemicals among HCWs and changes in the prevalence of work-related respiratory symptoms, but indicated early effects on ventilatory function among them. The study highlights the importance of periodic spirometry, proper work practices, and effective control measures to protect HCWs against potentially harmful workplace chemicals for disinfection and sterilization.
The aim of the present study was to assess and compare the individual adverse effects of bisphenol A (BPA) and octylphenol (OP) on the reproductive system of prepubertal male rats. Rats were exposed to BPA and OP at doses of 125 and 250 mg/kg/day, by gavage, for 90 days. At the end of the study, the testes, epididymis, prostate gland, and seminal vesicle were removed and examined histopathologically. Also, 3-β-hydroxysteroid dehydrogenase expressions were analyzed and serum testosterone and luteinizing hormone (LH) levels were measured. Sperm head count of caput epididymis was performed using a hemocytometer. Seminiferous and epididymal round tubules were evaluated for tubule diameter, lumen diameter, and height of tubule epithelium. There were significant increases in relative testes weights in BPA125, OP125, and OP250 groups compared with the control. Atrophic tubules, pyknotic tubules, combined tubules, congestion, vacuolization of Sertoli cell, cell debris in the lumen, tubules without sperm, and degeneration of tubules were noted in the tissue specimens obtained from the treatment groups compared with the control group. Sperm head counts were decreased in all treatment groups except for the low-dose BPA group. Testosterone (T) levels decreased in the BPA and high-dose OP treatment groups. LH levels increased in BPA treatment groups and the low-dose OP treatment group and decreased in the high-dose OP group. Epithelial height of high-dose BPA and OP treatment groups increased compared with the control group. Furthermore tubular height of low-dose BPA and high-dose OP groups increased with respect to control levels. In the OP250 treatment group, thyroxine hormone level was increased compared to other groups. Also, in the OP125 treatment group, triiodothyronine hormone level was increased compared with other groups.
The results of this study showed that BPA and OP affect the steroidogenic enzyme expression and T production in Leydig cells. In conclusion, BPA and OP have adverse effects on the male reproductive system of prepubertal rats.
Toluene is an organic solvent that is used in various industrial applications. Despite its usefulness, toluene has toxic effects on the brain and is a substance that is commonly abused. Toluene causes behavioral and functional abnormalities such as decreased memory capacity, cognitive impairment, and depression-like symptoms. However, the target sites and toxic mechanisms of inhaled toluene in the brain are poorly understood. In this study, we subjected Sprague-Dawley (SD) rats to acute high-level toluene exposure (7000 ppm) to investigate its neuronal toxicity, and in particular, its effect on neurogenesis in the hippocampus. In order to assay the effects of inhaled toluene on hippocampal neurogenesis, we measured the levels of neurogenesis markers Ki-67 and doublecortin (DCX) in the hippocampus 1, 2, 5, and 8 days after cessation of toluene exposure. In addition to assaying clinical signs, body weight, and bronchoalveolar lavage fluid, the liver, lungs, and kidneys were subjected to histopathological examination to investigate the toxic effects of high-level toluene exposure. Although abnormal neurological signs were observed after toluene exposure, these disappeared within 24 h and no toluene-related toxicological effects were observed in the liver, lungs, or kidneys. The animals exposed to toluene showed significantly decreased hippocampal neurogenesis, which persisted until the 8th and final day of measurement. Thus, acute high-level toluene exposure inhibited hippocampal neurogenesis and produced transient abnormal neurological signs, but did not produce toxicity in the other organs studied.
Exposure to chemicals is inevitable for certain occupational groups, particularly in industrial countries. Some cytogenetic tests such as comet assay are effectively utilized to screen genotoxic effects of these chemicals in humans. The purpose of this study has been to assess the DNA damage in construction painters’ lymphocytes using the comet assay.
Fourteen male construction painters with 1 year of required work experience were randomly selected from the list of Painter Union in Gonabad city, Iran. In addition, 14 healthy male non-painters were randomly selected as controls. The DNA damage degree was determined using a fluorescence microscope and CometScore software. The obtained data were analyzed employing independent t-test using SPSS software v. 14 at the significant level of p < 0.05.
All participants were non-smokers and non-alcoholics. No significant differences were found between the two groups in terms of age, weight, height, body mass index, and systolic and diastolic blood pressure. The DNA damage in the painter group was significantly greater than that of the control group. Tail length (µm) was 12.63 ± 6.54 versus 2.90 ± 0.84, tail DNA (%) was 4.33 ± 1.84 versus 1.29 ± 0.43, and tail moment (µm) was 1.85 ± 0.98 versus 0.14 ± 0.20 in painter and control groups (p < 0.001), respectively.
The chemicals used in oil paint may increase the DNA damage in painter blood lymphocytes.
Silica nanoparticles (SiNPs) are being used increasingly in biomedical and industrial fields; however, their adverse effects on human health have not been fully investigated. In this study, we focused on some of the toxicological aspects of SiNPs by studying oxidative stress and pro-inflammatory responses in the frontal cortex, corpus striatum and hippocampus regions of rat brain. Wistar rats were exposed to SiNPs of size 80 nm and 10 nm at a dose of 150 µg/50 µL phosphate-buffered saline/rat for 30 days. The results indicated a significant increase of lipid peroxide levels and hydrogen peroxide content in various regions of the treated rat brain. Moreover, these changes were accompanied with a significant decrease in the activities of manganese superoxide dismutase, glutathione reductase, catalase and reduced glutathione in different brain regions, suggesting impaired antioxidant defence system. Furthermore, SiNPs exposure not only increased messenger RNA (mRNA) and protein expression of nuclear factor-B (NF-B) but also significantly increased the mRNA and protein levels of tumour necrosis factor α (TNF-α), interleukin 1β (IL-1β) and monocyte chemoattractant protein 1 (MCP-1) in different regions of rat brain. Cumulatively, these data suggest that SiNPs induced the activation of NF-B and increased the expression of TNF-α, IL-1β and MCP-1 in rat brain, possibly via redox-sensitive cellular signalling pathways.
Hexavalent chromium (CrVI)-containing compounds, present in industrial settings and in the environment, are known as carcinogens and mutagens. The present study is designed to test the hypothesis that oxidative stress mediates CrVI-induced apoptosis in testis. Male Wistar rats received an intraperitoneal injection of potassium dichromate at doses of 1 and 2 mg kg–1. Superoxide anion production was assessed by the determination of the reduction of cytochrome c and iodonitrotetrazolium, lipid peroxidation (LPO), metallothioneins (MTs), and catalase (CAT) activity. Apoptosis was evaluated by DNA fragmentation detected by agarose gel electrophoresis. Germinal cells apoptosis was detected by toluidine blue staining. The expression of Bax and Bcl-2 proteins (Pts) was also investigated. After 15 days of treatment, an increase of LPO and MT levels occurred, while CAT activity was decreased. Testicular tissues of treated rats showed pronounced degradation of the DNA into oligonucleotides as seen in the typical electrophoretic DNA ladder pattern. Intense apoptosis was observed in germinal cells of Cr-exposed rats. Bax Pt expression was induced in spermatogonia and spermatocytes cells of CrVI-treated rats. In contrast, Bcl-2 Pt was occasionally observed in germ cells of CrVI-exposed rats. These results clearly suggest that CrVI subacute treatment causes oxidative stress in rat testis leading to apoptosis.
Zinc oxide nanoparticles (ZnONP) are manufactured on a large scale and can be found in a variety of consumer products, such as sunscreens, lotions, paints and food additives. Few studies have been carried out on its genotoxic potential and related mechanisms in whole organisms. In the present study, the in vivo genotoxic activity of ZnONP and its bulk form was assayed using the wing-spot test and comet assay in Drosophila melanogaster. Additionally, a lipid peroxidation analysis using the thiobarbituric acid assay was also performed. Results obtained with the wing-spot test showed a lack of genotoxic activity of both ZnO forms. However, when both particle sizes were tested in the comet assay using larvae haemocytes, a significant increase in DNA damage was observed for ZnONP treatments but only at the higher dose applied. In addition, the lipid peroxidation assay showed significant malondialdehyde (MDA) induction for both ZnO forms, but the induction of MDA for ZnONP was higher for the ZnO bulk, suggesting that the observed DNA strand breaks could be induced by mediated oxidative stress. The overall data suggest that the potential genotoxicity of ZnONP in Drosophila can be considered weak according to the lack of mutagenic and recombinogenic effects and the induction of primary DNA damage only at high toxic doses of ZnONP. This study is the first assessing the genotoxic and oxidative stress potential of nano and bulk ZnO particles in Drosophila.
Studies suggested that the conditioned medium of mesenchymal stem cells (MSC-CM) inhibited the increased apoptosis in various cells. However, there are no reports underlying the protection of MSC-CM against 2,5-hexanedione (HD)-induced apoptosis in neural cells. In the present study, the viability was observed in PC12 cells that received HD alone or with MSC-CM by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis was estimated by Hoechst 33342 staining and flow cytometry. Mitochondrial transmembrane potential was examined by rhodamine 123. Moreover, we investigated the expression of Bax and Bcl-2, cytochrome c translocation, and caspase 3 activity by real-time polymerase chain reaction, Western blot, and immunochemistry. Nerve growth factor (NGF) was examined in MSCs and MSC-CM. Our results showed that MSC-CM promoted cell survival and reduced apoptosis in HD-exposed PC12 cells. Moreover, MSC-CM significantly reversed disturbance of Bax and Bcl-2, ameliorated disruption of mitochondrial transmembrane potential, and reduced release of cytochrome c and activity of caspase 3 in HD-exposed PC12 cells. In the meantime, NGF was detected in MSCs and MSC-CM. These findings demonstrate that MSC-CM protects against HD-induced apoptosis in PC12 cells via inhibiting mitochondrial pathway. Our results indicate that NGF in MSC-CM may be involved in the protection of MSC-CM against HD-induced apoptosis. Our study clarifies the protection of MSC-CM on HD neurotoxicity and its underlying mechanism.
The aim of this study is to evaluate whether exposure to low concentrations of cadmium (Cd) can have effects on the thyroid hormone level of outdoor workers exposed to urban pollutants.
The study was conducted on a final sample of 277 individuals (184 males and 93 females). The environmental monitoring of Cd was evaluated through the use of portable dosimeters, while the biological monitoring was achieved through the assessment of urinary Cd and thyroid hormones. The total sample was divided according to sex and task. The Pearson’s correlation coefficient among the variables was calculated after subdivision on the basis of sex and task. The multiple linear regression was performed to take into account the major confounding factors.
Statistical tests showed a negative correlation between urinary Cd levels and free triiodothyronine and free thyroxine and a positive correlation between urinary Cd and thyroid-stimulating hormone levels.
Our early results seem to point out that occupational exposure to low concentrations of Cd present in urban air affects the thyroid hormone levels in exposed workers.
Ethylbenzene is an important industrial chemical, but its potential toxicity is a recent concern. Our previous study investigated the renal toxicity of ethylbenzene in vivo. Rat renal epithelial cells (NRK-52E cells) were incubated with 0, 30, 60, and 90 µmol/L of ethylbenzene for 24 h in vitro to investigate ethylbenzene-induced oxidative stress, apoptosis, and the expression of heme oxygenase 1 (HO-1) and nuclear factor (erythroid 2)-related factor 2 (Nrf2). The cell survival rate in the ethylbenzene-treated groups was significantly lower than the control group. Ethylbenzene significantly increased intracellular reactive oxygen species and apoptosis. Malondialdehyde levels were significantly elevated compared with the control group, while glutathione levels and glutathione peroxidase activities were decreased in ethylbenzene-treated groups. The activities of catalase and superoxide dismutase were also markedly reduced. A significant dose-dependent increase in HO-1 and Nrf2 messenger RNA expression levels was observed in ethylbenzene-treated groups compared with the control group. Similarly, ethylbenzene treatment enhanced protein expression of HO-1 and Nrf2 in a dose-dependent manner. Our results indicated that ethylbenzene induced oxidative stress, apoptosis, and upregulation of HO-1 and Nrf2 in NRK-52E cells, which contributes to ethylbenzene-induced renal toxicity.
The negative health effects caused by lead (Pb) exposure are widely recognized; however, the molecular mechanisms remain unknown. The aim of this study was to assess the effect of occupational Pb exposure on telomere length and to investigate the potential mechanisms leading to telomere shortening. A cohort of 334 male Pb smelters (exposed group) and 60 age-adjusted males unexposed to Pb (control group) were examined. Assessments of relative telomere length (rTL) and telomerase reverse transcriptase (TERT) gene expression were performed using quantitative real-time polymerase chain reactions. Assessments of whole blood Pb (B-Pb) and whole blood cadmium (B-Cd) concentrations and serum selenium concentration (S-Se) were performed using graphite furnace atomic absorption spectrometry. We analyzed total oxidation status (TOS), lipid hydroperoxides (LHPs), malonylodialdehyde levels in serum (MDA) and in erythrocyte hemolysates (MDA-hgb), and 8-hydroxy-deoxy-guanosine (8-OHdG). The Pb-exposed group had higher B-Pb values and shorter rTL than the control group. The arithmetic mean values calculated for B-Pb were 33 µg/dL versus 2.2 µg/dL (p < 0.0001), and the rTL values were 0.928 and 1.126 relative units (p = 0.001), respectively, for the Pb-exposed and control groups. The rTL was found to gradually shorten in response to the increasing levels of Pb exposure. The Pb-exposed group also demonstrated a higher level of oxidative stress than the control group, which was indicated by increased TOS and MDA-hgb values. rTL was negatively associated with parameters that indicated increased oxidative stress, including TOS (Spearman’s rank coefficient (r S) = –0.16; p < 0.01) and MDA-hgb (r S = –0.17; p < 0.001). No correlations were found between rTL and B-Cd and S-Se or smoking and MDA and LHP levels. Univariate analysis indicated that B-Pb was associated with decreased rTL (β =–0.0041; p = 0.0063) and that the association between B-Pb and rTL remained significant, even when adjusting for age (β = –0.0041; p = 0.0065) and in multivariable-adjusted model (β = –0.0042; p = 0.0063). In conclusion, occupational Pb exposure resulted in decreased rTL and may represent a mechanism that contributes to Pb-related diseases.
Pulmonary complications of exposure to sulfur mustard (SM) gas range from no effect or mild symptoms to severe bronchial stenosis. In the present study, the protective effect of vitamin E on the lung inflammation of SM-exposed guinea pigs was examined. Guinea pigs (n = 5 for each group) were exposed to ethanol (control group), 40 mg/m3 inhaled SM (SME group), SME treated with vitamin E (SME + E), SME treated with dexamethasone (SME + D), and SME treated with both treatments (SME + E + D). Pathological evaluation of the lung was done 14 days postexposure. The epithelial desquamation of trachea and other pathologic changes in the lung of the SME group were significantly higher than those in the control group. Furthermore, the pathological changes of trachea and lung in the SME + E and SME + E + D groups were significantly improved compared with those of SME group. In addition, the pathological changes of trachea and lung of SME + E and SME + E + D animals were significantly less than those of SME + D group.
In this study, we aimed to investigate the extent of genotoxic risk and the association between null GSTM1/GSTT1 and GSTP1 Ile105Val variants and cellular DNA damage, as measured by micronucleus (MN) assay in a group of agricultural workers from Denizli, Turkey. Peripheral blood samples were collected from 116 subjects, including 58 workers who were occupationally exposed to pesticides and 58 healthy unexposed controls. The MN frequencies of each individual were assessed by cytokinesis-blocked micronuclei assays on lymphocytes. Genotypes for different GST variants were determined using polymerase chain reaction-based methods. A significant 3.4-fold increase in MN frequency was observed in workers compared with the controls (p < 0.001). Among the GST genotypes, only the GSTM1 null genotype was found to be significantly associated with an increased MN frequency in workers (p = 0.01). Individuals with a concomitant null GSTM1/GSTT1 genotype demonstrated a significant (p = 0.01) increase in MN frequency compared with those with functional isozymes in the exposed worker group. The association of the GSTM1 null genotype with higher MN frequency suggests that it may be a modifier of genotoxic risk in individuals exposed to pesticides and may thus be a candidate susceptibility biomarker for human biomonitoring studies.
Exposure to arsenic and mercury is known to cause respiratory problems in both humans and animals. In this study, we elicit and compare maximum contraction caused by As(III) and Hg(II) when the pollutants are fully equilibrated with contractile machinery in resting mode. Hypercontraction of 27% and 69% was obtained following exposure of tracheal rings to 25 µM As(III) and 6 nM Hg(II) for 40 min, respectively. Co-incubation of tracheal rings with pollutants and verapamil, sodium nitroprusside or apocynin indicates that major contributors to As(III) and Hg(II) caused hypercontraction are reactive oxygen species (ROS) elevation and nitric oxide (NO) depletion. Changes in calcium influx have minor contribution in As(III) and Hg(II) caused increased contraction of tracheal tissues. Eugenol and carvone caused relaxation of 38% and 45% in pollutant unexposed rings, 56% and 49% in As(III)-exposed tracheal rings, and 54% and 47% in Hg(II)-exposed tracheal rings. Pathway delineation studies indicate that the major effect of eugenol originates from quenching of ROS whereas that of carvone originates from the blockage of extracellular calcium influx. Both molecules also show a minor stimulatory effect on NO generation. In line with their suggested mode of relaxation, eugenol is found to better ameliorate both As(III)- and Hg(II)-caused hypercontraction. Carvone, though a better relaxant than eugenol, comes out as poor ameliorator of both As(III)- and Hg(II)-caused hypercontraction, as the pathway on which it acts is not elevated following exposure to these pollutants.
Vinyl chloride monomer (VCM) is widely used in the production of polyvinyl chloride (PVC) plastics. VCM is recognized as a confirmed human and animal carcinogenic compound. Recent studies have reported poor health of plastic workers, even having exposure at concentrations below the permissible limit to VCM. There has not been any study regarding exposed workers to VCM in Iran. Similarly, no information exists as to the biological monitoring of such workers. The main purpose of this study was to conduct a thorough occupational and biological monitoring of Iranian plastic workers exposed to VCM.
A total of 100 workers from two plastic manufacturing plants (A and B) in Tehran along with 25 unexposed workers as controls were studied. The personal monitoring of all nonsmoking workers exposed to VCM at two plastic manufacturing plants (A and B) was performed in the morning shift (8 a.m. to 4 p.m.) according to the National Institute For Occupational Safety And Health method no. 1007.
Biological monitoring of workers was carried out through collection of exhaled breath of all exposed and control workers in Tedlar bags and with a subsequent analysis using gas chromatography–flame ionization detector.
Not only the mean occupational exposure of workers to VCM at plant A was higher than the respective threshold limit value but also the statistical significance was higher than workers at plant B. Similarly, VCM concentration in exhaled breath of workers at plant A was also statistically significantly higher than at plant B. Correlation of occupational exposure of all workers to vinyl chloride with its concentration in exhaled breath was statistically significant.
This is the first study on biological monitoring for exposed plastic workers to VCM using exhaled breath. On the basis of the results in this study, a novel method of biological monitoring of plastic workers was proposed.
Flumetralin, a synthetic plant growth regulator with herbicidal activity belonging to the 2,6-dinitroaniline class of chemicals, has been evaluated for its ability to induce genotoxicity in human peripheral blood lymphocytes (PBLs). The potential genotoxic and cytotoxic effects of flumetralin were investigated in vitro by chromosome aberration (CA) and cytokinesis-block micronucleus assays. Human PBLs were treated with 125, 250, 500, and 1000 µg/mL flumetralin for 24 and 48 h. Flumetralin statistically significantly increased the frequency of structural CAs at the three highest concentrations (250, 500, and 1000 µg/mL) for both treatment periods (24 and 48 h) when compared with both the negative and solvent controls. In addition, micronucleus formation was significantly induced at higher concentrations (250, 500, and 1000 µg/mL) for 24 h and at 125 and 500 µg/mL of flumetralin for the 48-h treatment period compared with the controls. Because of the excessive cytostatic effects of flumetralin, binuclear cells could not be detected sufficiently at the highest two concentrations (500 and 1000 µg/mL) for the 48-h treatment period. Furthermore, flumetralin significantly decreased the mitotic index and nuclear division index for all concentrations and treatment times compared with the control groups. The present results indicate that flumetralin was clastogenic and cytotoxic/cytostatic to human PBLs. This study presents the first report of the genotoxic and cytotoxic properties of flumetralin.
In this research, the removal of Sudan black B (SBB) by cadmium hydroxide nanowires loaded on activated carbon is described. After optimizing the variables involved, Langmuir, Freundlich, Tempkin, and Dubinin–Radushkevich models were applied to fit the experimental data. The adsorbent correlation coefficient and error analysis indicated the applicability of Langmuir model for the interpretation of equilibrium data. Different kinetic models were applied to analyze the time evolution of removal data. It was found that low quantity of adsorbent (<0.03 g) is capable of removal of large amount of SBB in reasonably short time (<40 min). The adsorption process was found to be described by both pseudo–second-order kinetics and interparticle diffusion mechanism. The effects of variables such as pH, amount of adsorbent, and contact time on batch adsorption process were investigated and optimized.
Metallothionein-1 (MT-1), cytochrome P450-2A (CYP2a) and other genes are involved in the detoxification of xenobiotics such as heavy metals and toxins. Changes in their expression precede overt toxic effects and can serve as a marker for exposure to pollutants. We used a mouse experimental system and quantitative reverse transcription polymerase chain reaction to determine changes in gene expression and the direction of change, in response to exposure to lead acetate (LA) and waste water (WW) from an industrial area in Ibadan. MT-1 and CYP2a5 genes were quickly and highly induced at different exposure periods and concentrations. MT-1 was mostly downregulated by the LA exposure, but upregulated by several folds on exposure to WW. CYP2a5 expression was mostly downregulated with LA exposure. The optimum expression of MT-1 and CYP2a5 genes induced by both LA and WW was at 48 h. We conclude that rapid assays to determine the direction of change in the expression of MT-1 and CYP2a5 could be a fast and reliable method in developing countries for screening humans exposed to pollutants from industrial waste.
Formaldehyde (FA), a ubiquitous environmental pollutant, has long been suspected of causing adverse male reproductive effects. However, the molecular and cellular mechanisms underlying this phenomenon remain elusive. The overall aim of this study is to clarify the role of mammalian target of rapamycin (mTOR) in male reproductive injuries induced by FA exposure, by which we can further understand the molecular mechanism of FA male reproductive toxicity. In this study, immunohistochemistry, Western blotting, and reverse transcription polymerase chain reaction analysis were used to detect the expression of mTOR molecule in testicular tissues. We found that FA exposure inhibits the expression of mTOR in a dose-dependent manner. Combined with our earlier finding, we found the decreasing expression of mTOR in testicular tissue were consistent with the changes of testicular structure and autophagy levels. In summary, our data suggested that mTOR molecule might be involved in male reproductive injuries induced by FA exposure.
Occupational lead (Pb) exposure remains a significant concern for workers in Turkey. Health hazards of Pb exposure have been investigated in various test systems, but results regarding its potential genotoxic effects on exposed populations are contradictory. In this study, a control group and an exposed group were studied, each consisting of 25 male subjects. Blood lead levels (BLLs) were estimated by graphite furnace atomic absorption spectrometry. Genotoxic effects of Pb exposure were studied in leukocytes by comet and challenge assays. The effect of Pb exposure to DNA repair capacity was evaluated following in vitro hydrogen peroxide exposure. Pb-exposed workers had significantly higher BLLs than the control group (p < 0.01). DNA damage in exposed workers had a significantly higher percentage of DNA in tail than the control group (p < 0.05). In the challenge assay, it was found that the mean DNA% repair capacity was significantly decreased in Pb-exposed workers (p < 0.01). The results indicated that occupational Pb exposure is associated with DNA damage and causes decrease in DNA% repair capacity, indicating a potential health concern for occupationally Pb-exposed populations.
Seafood industry workers exhibit increased prevalence of respiratory symptoms due to exposure to bioaerosols containing a mixture of bioactive agents. In this study, a human pulmonary epithelial cell model (A549) was exposed to mixtures of bacterial lipopolysaccharide (LPS) and protease-activated receptor-2 (PAR-2) agonists H-Ser-Leu-Ile-Gly-Lys-Val-NH2 (SLIGKV-NH2), purified salmon (Salmo salar) trypsin or purified king crab (Paralithodes camtschaticus) trypsin. The inflammatory response was measured based on nuclear factor-kappa B (NF-B) activation of transcription in a luciferase reporter gene assay and interleukin 8 (IL-8) secretion in an enzyme-linked immunosorbent assay. We observed that mixtures of SLIGKV-NH2 or trypsins with LPS augmented the activation of NF-B and secretion of IL-8. The effect on IL-8 secretion was synergistic when both trypsins and LPS were used in the lower concentration range. The results demonstrate that exposure to mixtures of agents that are relevant to seafood industry workplaces may lead to increased inflammatory signalling compared with exposure to the individual agents alone. Furthermore, the results indicate that synergism may occur with the combined exposure to seafood trypsins and LPS and is most likely to occur when exposure to either agent is low.
This study aims to assess the effect of low oral dose of bisphenol A (BPA) on proliferation of ventral prostate (VP) and expression of related genes in adult rats. Three-month-old male Sprague Dawley rats were treated daily with BPA (10, 30, or 90 µg/kg, per os), 17β-estradiol (E2, 10.0 µg/kg, subcutaneously), or vehicle for 4 weeks. Treatment with 10 µg/kg BPA resulted in increased animal weight and VP epithelial height compared with the controls (p < 0.01), while such effects were less pronounced in higher BPA doses. Treatment with E2 showed opposite effects, with significantly decreased animal weight and VP epithelial height (p < 0.01). Interestingly, BPA increased serum E2 and reduced testosterone levels and significantly increased the estrogen to androgen ratio (p < 0.05). In addition, BPA slightly increased dihydrotestosterone (DHT) levels. Immunohistochemistry data showed that BPA significantly upregulated proliferating cell nuclear antigen expression (p < 0.01). Furthermore, microarray and reverse transcription polymerase chain reaction analyses showed that BPA induced upregulation of prostaglandin D2 synthase (Ptgds), Fas, Pbef1, and complement factor B (Cfb)as well as downregulation of Pttg1 and Fabp4 in the VP. These results indicated that environmental exposure to low doses of BPA may induce proliferation of VP in adult rats by increasing the estrogen to androgen ratio and upregulating expression of Ptgds to promote production of DHT.
Welding is used extensively in different industries. Welders are always at a risk of exposure to a number of gases and metal-containing fumes in their respective microenvironments in which they work. Welding fumes consist of a wide range of complex metal oxide particles which can deposit in different parts of their bodies causing serious health problems. In the present study, 35 welders (age: 33.80 ± 1.04 years) from two iron-based industries have been assessed for DNA damage in peripheral blood lymphocytes using single-cell gel electrophoresis. An equal number of subjects (N = 35; age: 30.40 ± 1.51 years) matched to exposed subjects with respect to sex, age, socioeconomic status, smoking, and alcoholic habits were taken as controls. The results revealed that the damaged cell frequency (DCF) and mean comet tail length (CTL) in welders were significantly higher as compared to the controls (DCF: 69.74 ± 1.68 vs. 31.14 ± 1.67 and CTL: 29.21 ± 1.48 vs. 1.47 ± 0.08; p < 0.05). The effect of confounding factors such as age, duration of exposure, smoking, and drinking habits was also studied. Blood lead levels also showed a positive correlation with duration of exposure and CTL, and the overall results indicated an increased genetic damage as an index of genotoxicity in workers occupationally engaged in welding microenvironments.
This study was carried out to find out whether exposure to environmentally relevant concentration of chlorpyrifos (CP) modulates reproductive competence. To understand this, eight adult male and eight adult female zebrafish (Danio rerio) were exposed to 200 µg/L of CP for 24, 48, 72, and 96 h. Vitellogenin levels did not show much change in female fish, whereas in male the levels increased with increasing exposure time thereby indicating estrogenecity of the toxicant. Attenuation of serum 11-ketotestosterone in male and serum 17β-estradiol in female was noticed in the exposed fish and thus signified interference of CP in the reproductive endocrine system. Structural damage common to both the gonads was vacuolization. Elongation of seminiferous tubules in testes and atretic follicles in ovary was also observed.
T-2 toxin is one of the mycotoxins, a group of type A trichothecenes produced by several fungal genera including Fusarium species, which may lead to the decrease of testosterone secretion in primary Leydig cells derived from mouse testis. The previous study demonstrated T-2 toxin decrease the testosterone biosynthesis in the primary Leydig cells derived from the mouse testis directly. In this study, we further examined the direct biological effects of T-2 toxin on the process of steroidogenesis, primarily in Leydig cells of mice. Leydig cells of mature mouse were purified by Percoll gradient centrifugation and the cell purity was determined by 3β-hydroxysteroid dehydrogenase (3β-HSD) staining. To examine the decrease in T-2 toxin-induced testosterone secretion, we measured the transcription level of three key steroidogenic enzymes including 3β-HSD-1, cytochrome P450 side-chain cleavage (P450scc) enzyme, and steroidogenic acute regulatory (StAR) protein in T-2 toxin/human chorionic gonadotropin (hCG) co-treated cells. Our previous study showed that T-2 toxin (10–7, 10–8, and 10–9 M) significantly suppressed hCG (10 ng/ml)-induced testosterone secretion. The studies demonstrated that the suppressive effect is correlated with a decrease in the level of transcription of 3β-HSD-1, P450scc, and StAR (p < 0.05).
Lanthanum (La) appears to impair learning and memory and increase the toxicity of excitatory amino acids in the central nervous system. The mechanism underlying excitotoxicity induced by La is still unclear. The purpose of this study was to investigate the hippocampal impairment of La exposure and possible mechanism involving the glutamate–nitric oxide (NO)–3'-5'-cyclic guanosine monophosphate (cGMP) pathway. In this study, lactating rats were exposed to 0, 0.25, 0.50, and 1.0% lanthanum chloride (LaCl3) in drinking water, respectively. Their offsprings were exposed to LaCl3 by parental lactation and then administrated with 0, 0.25, 0.50, and 1.0% LaCl3 in drinking water for 1 month. The results showed that La exposure impaired the neuronal ultrastructure and significantly increased the glutamate level, intracellular calcium ion concentrations, and NR1 and NR2B expression in the hippocampi. La exposure significantly enhanced messenger RNA expression and activity levels of inducible NO synthase and increased NO and cGMP levels in the hippocampi in a dose-dependent manner. These results indicate that the mechanism underlying excitotoxicity induced by La is possibly due to alterations of the glutamate–NO–cGMP signaling pathway in the hippocampus. The study provides new findings that may help prevent and improve treatments for La-induced neurotoxicity.
In this study, biological exposure indicators were used to assess the exposure of workers to cadmium (Cd), lead (Pb), manganese (Mn), and nickel (Ni) in nonferrous metal smelters.
A total of 273 male participants (178 exposed and 95 nonexposed control group), working in nonferrous metal foundries located in southern Brazil, were evaluated based on biological indicators, environmental levels, and different types of work performed by the participants. Blood Pb (BPb), urinary Cd (UCd), urinary Mn (UMn), and urinary Ni (UNi) levels were quantified by graphite furnace atomic absorption spectrometry with Zeeman background correction.
Significant differences between the exposed and nonexposed groups were observed for all of the analyzed elements. The average levels of BPb were higher than the recommended occupational exposure level. Relatively low concentrations were found for UCd, UMn, and UNi.
Although metal production is an important segment of the Brazilian economy, information related to employee health in this sector is scarce. The environmental levels are determinant in occupational exposure in foundries. In companies where air levels of Pb, Cd, and Mn were above the established limits, the different types of activity did not represent an important influence on the biological levels found among workers. In situations with low air levels of these metals, the workers from the "melting" sector were actually more vulnerable.
Millions of pounds of polychlorinated biphenyl (PCB) compounds have been produced in multiple countries for industrial applications over the last several decades. PCB exposure induces various adverse health effects in animals and humans. Environmental and occupational exposures to PCBs have been associated with liver, kidney, endocrine, and neurodevelopmental adverse effects. We have collected and reviewed animal and human data cited in the US National Library of Medicine from 2000 to 2010. In brief, our review shows new evidence, that is, in animal studies, exposure to one of the PCBs, A1221, induces a significant alteration of serum luteinizing hormone. The effects were more profound in the F2 generation, particularly with respect to fluctuations in hormones and reproductive tract tissues across the estrous cycle. Morphological analyses of brain tissue from rats exposed to A1254 confirmed the results of an earlier work which showed that the relative size of the intra- and infrapyramidal (II-P) mossy fibers was smaller than that in the controls and also reduction in growth was selective for the II-P mossy fibers. PCB exposure increased anogenital distance and prostate size but decreased epididymal weight, epididymal sperm count, and motile epididymal sperm count. No effects were observed on testicular weight or size. The epidemiological data showed an association between diabetes mellitus prevalence and elevated concentrations of PCB 153. Additionally, prenatal PCB exposure studies were associated with a smaller thymic index at birth and could adversely affect immune responses to childhood vaccinations and resistance to respiratory infections. PCB exposure was also reported to adversely affect enamel development in children in a dose-dependent manner. Because PCBs and their metabolites are potential health hazards, understanding the risk factors associated with individual PCBs, PCB mixtures, and PCB metabolites is important. PCB exposures of vulnerable populations (pregnant women, fetuses, infants, and children) are of particular concern because of heightened sensitivity during this period of brain development.
Trichloroethylene (TCE), a halogenated organic solvent widely used in industries, is known to cause severe hepatotoxicity. However, the mechanisms underlying TCE hepatotoxicity are still not well understood. It is predicted that membrane proteins are responsible for key biological functions, and recent studies have revealed that TCE exposure can induce abnormal levels of membrane proteins in body fluids and cultured cells. The aim of this study is to investigate the TCE-induced alterations of membrane proteins profiles in human hepatic L-02 liver cells. A comparative membrane proteomics analysis was performed in combination with two-dimensional fluorescence difference gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry. A total of 15 proteins were identified as differentially expressed (4 upregulated and 11 downregulated) between TCE-treated cells and normal controls. Among this, 14 of them are suggested as membrane-associated proteins by their transmembrane domain and/or subcellular location. Furthermore, the differential expression of β subunit of adenosine triphosphate synthase (ATP5B) and prolyl 4-hydroxylase, β polypeptide (P4HB) were verified by Western blot analysis in TCE-treated L-02 cells. Our work not only reveals the association between TCE exposure and altered expression of membrane proteins but also provides a novel strategy to discover membrane biomarkers and elucidate the potential mechanisms involving with membrane proteins response to chemical-induced toxic effect.
Formaldehyde (FA) is a chemical widely used in the furniture industry and has been classified as a potential human carcinogen. The purpose of this study was to evaluate the occupational exposure of workers to FA at a furniture manufacturing facility and the relationship between environmental concentrations of FA, formic acid concentration in urine, and DNA damage. The sample consisted of 46 workers exposed to FA and a control group of 45 individuals with no history of occupational exposure. Environmental concentrations of FA were determined by high-performance liquid chromatography. Urinary formic acid concentrations were determined by gas chromatography with flame ionization detector. DNA damage was evaluated by the micronucleus (MN) test performed in exfoliated buccal cells and comet assay with venous blood. The 8-h time-weighted average of FA environmental concentration ranged from 0.03 ppm to 0.09 ppm at the plant, and the control group was exposed to a mean concentration of 0.012 ppm. Workers exposed to higher environmental FA concentrations had urinary formic acid concentrations significantly different from those of controls (31.85 mg L–1 vs. 19.35 mg L–, p ≤ 0.01 Mann–Whitney test). Significant differences were found between control and exposed groups for the following parameters: damage frequency and damage index in the comet assay, frequency of binucleated cells in the MN test, and formic acid concentration in urine. The frequency of micronuclei, nuclear buds, and karyorrhexis did not differ between groups. There was a positive correlation between environmental concentrations of FA and damage frequency (Spearman’s rank correlation coefficient [r s] = 0.24), damage index (r s = 0.21), binucleated cells (r s = 0.34), and urinary formic acid concentration (r s = 0.63). The results indicate that, although workers in the furniture manufacturing facility were exposed to low environmental levels of FA, this agent contributes to the observed increase in cytogenetic damage. In addition, urinary formic acid concentrations correlated strongly with occupational exposure to FA.
Little research has been done on the relationships between chromium exposure, skin barrier function, and other hygienic habits in cement workers. Our purpose was to investigate chromium-induced skin barrier disruption due to cement exposure among cement workers. One hundred and eight cement workers were recruited in this study. Urinary chromium concentration was used to characterize exposure levels. The biological exposure index was used to separate high and low chromium exposure. Transepidermal water loss (TEWL) was used to assess the skin barrier function. TEWL was significantly increased in workers with high chromium exposure levels than those with low chromium exposure levels (p = 0.048). A positive correlation was also found between urinary chromium concentration and TEWL (R = 0.28, p = 0.004). After adjusting for smoking status and glove use, a significant correlation between urinary chromium concentrations and TEWL remained. Moreover, workers who smoked and had a high chromium exposure had significantly increased TEWL compared to nonsmokers with low chromium exposure (p = 0.01). Skin barrier function of cement workers may have been disrupted by chromium in cement, and smoking might significantly enhance such skin barrier perturbation with chromium exposure. Decreased chromium skin exposure and smoking cessation should be encouraged at work.
Microcystins (MCs) are the most potent toxins that can be produced by cyanobacteria in drinking water supplies. This study investigated the abundance of toxin-producing algae in 11 drinking water treatment plants (DWTPs). A total of 26 different algal taxa were identified in treated water, from which 12% were blue green, 29% were green, and 59% were diatoms. MC levels maintained strong positive correlations with number of cyanophycean cells in raw and treated water of different DWTPs. Furthermore, the efficiency of various algal-based adsorbent columns used for the removal of these toxins was evaluated. The MCs was adsorbed in the following order: mixed algal-activated carbon (AAC) ≥ individual AAC > mixed algal powder > individual algal powder. The results showed that the AAC had the highest efficient columns capable of removing 100% dissolved MCs from drinking water samples, thereby offering an economically feasible technology for efficient removal and recovery of MCs in DWTPs.
The concentration of chromium in the blood (CrB) has been confirmed as a biomarker for occupational chromium exposure, but its biological exposure indices (BEIs) are still unclear, so we collected data from the years 2006 and 2008 (Shandong Province, China) to analyze the relationship between the concentration of chromium in the air (CrA) of the workplaces and CrB to establish a reference value of CrB for biological monitoring of occupational workers. The levels of the indicators for nasal injury, kidney (β2 microglobulin (β2-MG)), and genetic damages (8-hydroxy-deoxyguanosine (8-OHdG) and micronucleus (MN)) were measured in all subjects of the year 2011 (Henan Province, China) to verify the protective effect in this reference value of CrB. Compared with the control groups, the concentrations of CrA and CrB in chromium exposed groups were significantly higher (P < 0.05). Positive correlations were found between CrA and CrB in chromium exposed groups (r 2006 = 0.60, r 2008 = 0.35) in the years 2006 and 2008. According to the occupational exposure limitation of CrA (50 μg/m3, China), the reference value of CrB was recommended to 20 μg/L. The levels of nasal injury, β2-MG, 8-OhdG, and MN were not significantly different between the low chromium exposed group (CrB ≤ 20 μg/L) and the control group, while the levels of β2-MG, 8-OHdG, and MN were statistically different in the high chromium exposed group than that in the control group. This research proved that only in occupational workers, CrB could be used as a biomarker to show chromium exposure in the environment. The recommended reference value of CrB was 20 μg/L.
In this study, the mutagenicity and genotoxicity of indium tin oxide (ITO) nanomaterial were assessed using two standard genotoxicity assays, the Salmonella reverse mutation assay (Ames test) and the in vitro micronucleus (MN) assay. Seven different concentrations (12.5, 25, 50, 75, 100, 125, and 150 µg/plate) of this nanomaterial were tested using the Ames test on the TA98 and TA100 strains in the presence and absence of the S9 mixture. At all the concentrations tested, this substance did not significantly increase the number of revertant colonies compared with the control with or without S9 mixture. The genotoxic effects of ITO were investigated in human peripheral lymphocytes treated with 125, 250, 500, and 750 µg/ml concentrations of this substance for 24- and 48-h treatment periods using an MN test. Nuclear division index (NDI) was also calculated in order to determine the cytotoxicity of ITO. It was determined that ITO increased MN frequency in the 750 µg/ml concentration in 24- and 48-h treatments. In addition, ITO dose dependently decreased the NDI significantly for two treatment periods.
Hexavalent chromium (Cr(VI)) is an environmental contaminant that is associated with reproductive abnormalities in both humans and animals. In the present study, we evaluated the cytotoxic effect of Cr(VI) on sperm function and subsequent embryo development after in vitro fertilization (IVF). Sperm obtained from BDF1 male mice were treated with potassium dichromate (0, 3.125, 6.25, 12.5, 25, or 50 μM) for 3 h. Cr(VI) significantly decreased sperm viability and acrosome reaction with increasing dose. These Cr(VI)-treated sperms were further used for IVF of oocytes obtained from BDF1 female mice. Results showed that Cr(VI)-treated sperm caused a significant reduction in IVF success, higher developmental arrest at the two-cell stage of embryos, and delayed blastocyst formation with increasing dose. In particular, most blastocysts from the Cr(VI)-treated sperm resulted in hatching failure as well as decreased inner cell mass and trophectoderm (TE). Furthermore, blastocysts obtained from Cr(VI)-treated sperm showed lower expression of not only TE-associated genes (eomes, cdx2, and krt8) but also pluripotent marker genes (sox2, pou5f1, and klf4) that are responsible for further embryo development of blastocyst embryos. The results of our current study showed that Cr(VI)-treated sperm had negative effects on oocyte fertilization and subsequent embryo development.
Bisphenol A (BPA), an endocrine-disrupting chemical, is widely used in the manufacture of polycarbonated plastics and epoxy resins and line metal beverage cans. Growing evidence suggests that BPA acts directly on neuronal functions as it is lipophilic and could accumulate in the brain. The present study aims to investigate the effect of two doses of BPA (10 mg/kg for 6 and 10 weeks and 25 mg/kg for 6 weeks) on excitatory (glutamate and aspartate) and inhibitory (-aminobutyric acid, glycine, and taurine) amino acid neurotransmitter levels in the cortex and hippocampus. This study extends to investigate the effect of BPA on acetylcholinesterase (AchE) activity and some oxidative stress parameters in the two regions. In the cortex, a significant increase in the excitatory and a significant decrease in the inhibitory amino acids occurred after BPA (10 mg/kg for 10 weeks and 25 mg/kg for 6 weeks). This was accompanied by a significant increase in lipid peroxidation, nitric oxide, and reduced glutathione after 6 weeks of BPA (25 mg/kg). In the hippocampus, a significant increase in the excitatory and inhibitory amino acid neurotransmitters occurred after 6 weeks of BPA. Hippocampal lipid peroxidation increased significantly after BPA exposure and hippocampal reduced glutathione increased significantly after 6 weeks of BPA exposure (10 mg/kg). BPA induced a significant increase in cortical and hippocampal AchE activity. The present neurochemical changes in the cortex and hippocampus suggest that BPA induced a state of excitotoxicity and oxidative stress. This may raise concerns about the exposure of humans to BPA due to its wide applications in industry.
The aim of this study was to reveal the effects of aluminum chloride (AlCl3) on the hepatic metabolism function and trace elements’ distribution. Two hundred healthy male chickens (1 day old) were intraperitoneally administered with AlCl3 (0, 18.31, 27.47, and 36.62 mg kg–1 day–1 of Al3+) consecutively for 3 days. Then the chickens were allowed to rest for 1 day. The cycle lasted four days. The cycle was repeated 15 times (60 days). The contents of serum total protein (TP), albumin (ALB), total bilirubin (TBI), direct bilirubin (DBI), hepatic aluminum (Al), copper (Cu), iron (Fe), and zinc (Zn) were examined. The results showed that the contents of serum TP and ALB and hepatic Fe and Zn decreased and the contents of serum TBI and DBI and hepatic Al and Cu increased in the chickens with AlCl3. This indicates that chronic administration of AlCl3 impairs the hepatic metabolism function and disorders the hepatic trace elements’ distribution.
For the purposes of the present study, the protective effect of prostaglandin E1 (PGE1) on lung injury following renal ischemia–reperfusion (RIR) was investigated. Adult male rats were divided into four groups, namely, (I) control rats given physiological saline; (II) rats given PGE1 (20 μg/kg, intravenously); (III) rats subjected to RIR; and (IV) rats subjected to RIR given PGE1 30 min prior to ischemia and just before reperfusion. The right nephrectomy was performed in the RIR model. The left renal pedicle was occluded for 60 min to induce ischemia and then the left kidney was subjected to reperfusion for 60 min. The lungs of rats were used for microscopic and biochemical analyses. Although rats subjected to RIR did not exhibit heavy degenerative alterations in the lung structure, they possessed pulmonary interstitial edema. Lung glutathione levels and catalase, superoxide dismutase, glutathione peroxidase, and tissue factor (TF) activities were decreased in rats subjected to RIR, while lung lipid peroxidation, myeloperoxidase (MPO), xanthine oxidase and serum lactate dehydrogenase (LDH) activities, and blood urea and serum creatinine levels were increased in these rats when compared with the control group. PGE1 treatments resulted in the regression of oxidative stress via induction of antioxidant system, the decreased MPO and LDH activities, the reduced urea and creatinine levels, and the induced TF activity in rats subjected to RIR, while edema still remained permanent. We conclude that PGE1 may be useful in preventing lung injury with the exception of edema that occurred as a result of RIR in rats.
Several studies have explored the hypothesis that low blood lead (PbB) and high noise levels may be associated with an increased risk of hypertension. To assess the possible relationship between occupational exposure to lead (Pb) and noise and elevated blood pressure, we studied 105 workers (age: 41.27 ± 6.25 years and length of employment: 4.12 ± 5.33 years) employed in a Pb battery recycling plant by measuring A-weighted equivalent sound level, PbB, -aminolevulinic acid dehydratase (ALAD) activity and zinc protoporphyrin (ZPP) levels and systolic and diastolic blood pressure (SBP and DBP). Results showed that occupational exposure to higher ambient Pb and noise levels was related to slightly increased SBP and DBP. PbB values correlated significantly with SBP and DBP, whereas noise levels correlated neither with SBP nor with DBP. Furthermore, workers exposed to higher ambient Pb had higher PbB and ZPP and showed more decreased ALAD activity. Blood pressure does not correlate with noise exposure but only with PbB concentration.
The activities of antioxidant enzymes and the levels of glutathione (GSH) and malondialdehyde (MDA) were determined when freshwater planarian Dugesia japonica was exposed to different concentrations of 1-octyl-3-methylimidazolium bromide ([C8mim]Br) for one, three, and five days. The results showed that superoxide dismutase (SOD) activity began to increase in all treated groups after three days of exposure, while catalase (CAT) activity was inhibited after the first day, but increased notably on the fifth day except for the lowest concentration group. The activity of glutathione peroxidase (GPX) was induced from the first day of exposure and increased significantly after five days in all treated groups. During the experiment, the levels of intracellular GSH in all treated groups were higher than that of the control group. Changes in MDA suggest that [C8mim]Br is toxic to D. japonica and may result in lipid peroxidation in planarian. Our results also indicate that GPX as well as GSH seem to be more sensitive biomarkers of oxidative stress compared with SOD and CAT.
The growth of the influence of anthropogenic factors aimed on the improvement of human life has its side effect, for example, living organisms receive increasing exposure to toxic mercuric compounds. Experimental data show that mercury (Hg) salts are able to induce systemic autoimmunity in rodents. This Hg-induced autoimmune process (HgIA) is characterized by T cell-dependent polyclonal activation of B lymphocytes, increased level of serum immunoglobulin G1 (IgG1) and immunoglobulin E (IgE), production of antinucleolar autoantibodies (ANoA), and immune complex deposition in multiple organs. HgIA in mice is used as a model of human systemic autoimmune disorders. However, the dose of mercuric chloride (HgCl2) usually used in laboratory mice to induce HgIA is above the allowable limit for everyday levels of Hg exposure in humans. So, we decided to determine the lowest dose of HgCl2 that is able to trigger autoimmunity in outbred Carworth Farms Swiss Webster (CFW) mice not genetically prone to HgIA development. The lowest dose (50 µg/kg body weight (b.w.)/week) was chosen to match the World Health Organization provisional weekly tolerable intake of total Hg for humans. We also tested HgCl2 at 500 and 1500 µg/kg b.w./week (6.5- and 2-fold less than usually used for induction of HgIA in mice). We found that even the lowest dose of Hg resulted in a statistically significant increase in serum level of IgG1 after 8 weeks of treatment. HgCl2 in doses 500 and 1500 µg/kg b.w./week resulted in a significant increase in serum level of IgG1 after 4 weeks of treatment, followed by ANoA production. Sera of HgCl2-treated mice stained the regions in which the major autoantigen in HgIA, fibrillarin, was revealed. These results suggest that low doses of Hg are able to induce the main features of HgIA in genetically heterozygous mice, and that humans chronically exposed to low doses of Hg may be at risk of autoimmunity induction regardless of their genetic background.
To investigate the contributions and underlying molecular mechanisms of annexin A5 toward silica-induced pulmonary fibrosis.
Male C57BL/6 mice were randomly divided into three groups and instilled intratracheally with silica, saline, or air. Mice were euthanized at 3, 7, 14, or 28 days following treatment. Annexin A5 levels in serum and lung tissues were detected by enzyme-linked immunosorbant assay (ELISA) assays or Western blots. The association of annexin A5 levels with silica-induced lung fibrosis was further investigated in the macrophage cell line, RAW264.7. Following exposure of these cells to silica at a concentration of 200 μg/ml for 6 or 12 h, the expression levels of transforming growth factor β1 (TGF-β1), interleukin 1α (IL-1α), Fas ligand (FasL), and their downstream targets were evaluated by Western blots. Furthermore, annexin A5 and FasL were knocked down by small interfering ribonucleic acid (siRNA) and TGF-β1 secretion into the cell culture medium was measured by ELISA assays or Western blots.
Mice treated with silica demonstrated lung fibrosis at 28 days following exposure, whereas, in controls, only mild and transient inflammation was evident at day 3 and day 7 postinstillation and was not present at day 14. Furthermore, silica-exposed mice exhibited significantly (p < 0.05) elevated levels of annexin A5 in serum and lung tissues, relative to control groups. Consistent with these findings, silica exposure of RAW264.7 cells for 6 or 12 h, led to an annexin A5-dependent increase in the expression levels of TGF-β1, IL-1α, FasL, and their downstream target molecules. These silica-induced changes were reversed by siRNA-mediated knockdown of annexin A5, but downregulation of FasL led to increased annexin A5 expression and reduced levels of TGF-β1, IL-1α, and FasL downstream target molecules.
These findings define a role of annexin A5 in promoting macrophage activation via Fas/FasL pathways in silica-induced lung fibrosis.
The nature of occupational risks and hazards in industries that produce or use synthetic amorphous silica (SAS) nanoparticles is still under discussion. Manufactured SAS occur in amorphous form and can be divided into two main types according to the production process, namely, pyrogenic silica (powder) and precipitated silica (powder, gel or colloid). The physical and chemical properties of SAS may vary in terms of particle size, surface area, agglomeration state or purity, and differences in their toxicity potential might therefore be expected. The aim of this study was to compare the cytotoxicity and genotoxicity of representative manufactured SAS samples in Chinese hamster lung fibroblasts (V79 cells). Five samples from industrial SAS producers were evaluated, that is, two pyrogenic SAS powders (with primary particle sizes of 20 nm and 25/70 nm), one precipitated SAS powder (20 nm) and two precipitated SAS colloids (15 and 40/80 nm). V79 cell cultures were treated with different concentrations of SAS pre-dispersed in bovine serum albumin –water medium. Pyr (pyrogenic) 20, Pre (precipitated) 20 and Col (colloid) 15 significantly decreased the cell viability after 24 h of exposure, whilst Pyr 25/70 and Col 40/80 had negligible effects. The cytotoxicity of Pyr 20, Pre 20 and Col 15 was revealed by the induction of apoptosis, and Pyr 20 and Col 15 also produced DNA damage. However, none of the SAS samples generated intracellular reactive oxidative species, micronuclei or genomic mutations in V79 cells after 24 h of exposure. Overall, the results of this study show that pyrogenic, precipitated and colloidal manufactured SAS of around 20 nm primary particle size can produce significant cytotoxic and genotoxic effects in V79 cells. In contrast, the coarser-grained pyrogenic and colloid SAS (approximately 50 nm) yielded negligible toxicity, despite having been manufactured by same processes as their finer-grained equivalents. To explain these differences, the influence of particle agglomeration and oxidative species formation is discussed.
This study focuses on investigating the possible protective effect of sodium selenite (Na2SeO3) and/or vitamin E against mercuric chloride (HgCl2)-induced hepatotoxicity in rat. Male rats were given HgCl2 (1 mg/kg body weight (bw)) and HgCl2 plus Na2SeO3 (0.25 mg/kg bw) and/or vitamin E (100 mg/kg bw) daily via gavage for 4 weeks. HgCl2-treated groups had significantly higher white blood cell and thrombocyte counts than the control group. Serum activities of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, -glutamyl-transferase, and lactate dehydrogenase significantly increased and serum levels of total protein, albumin, triglyceride, total cholesterol, and low-density lipoprotein cholesterol significantly decreased in the HgCl2-treated groups compared with control group. Malondialdehyde level significantly increased and superoxide dismutase, catalase, and glutathione peroxidase activities decreased in liver tissue of HgCl2-treated rats. Also, HgCl2 exposure resulted in histopathological changes. Supplementation of Na2SeO3 and/or vitamin E provided partial protection in hematological and biochemical parameters that were altered by HgCl2. As a result, Na2SeO3 and/or vitamin E significantly reduced HgCl2-induced hepatotoxicity, but not protected completely.
Heavy metal-resistant bacteria can be efficient bioremediators of metals and may provide an alternative or additional method to conventional methods of metal removal. In this study, 10 bacterial isolates were isolated from soil samples of a sugar industry, located at Peshawar, Pakistan. Morphological, physiological, and biochemical characteristics of these isolates were observed. Sequence analysis (16S ribosomal RNA) revealed that isolated strains were closely related to the species belonging to the genera Pseudomonas, Arthrobacter, Exiguobacterium, Citrobacter, and Enterobacter. Bacterial isolates were resistant with a minimum inhibitory concentration (500–900 ppm) to lead ion (Pb2+), (500–600 ppm) nickel ion (Ni2+), (500–800 ppm) copper ion (Cu2+), and (600–800 ppm) chromium ion (Cr3+) in solid media. Furthermore, biosorption of metals proved considerable removal of heavy metals by isolated metal-resistant strains. Pseudomonas sp. reduced 37% (Pb2+), 32% (Ni2+), 29% (Cu2+), and 32% (Cr3+) and was thus found to be most effective, whereas Enterobacter sp. reduced 19% (Pb2+), 7% (Ni2+), 14% (Cu2+), and 21% (Cr3+) and was found to be least effective. While average reduction of Pb2+, Ni2+, Cu2+, and Cr3+ by Citrobacter sp. was found to be 24%, 18%, 23%, and 27%, respectively, among recognized species. This study revealed that Pseudomonas sp. may provide a new microbial community that can be used for enhanced remediation of contaminated environment.
N-Acetylcysteine (NAC) could be included in protocols designed for the treatment of lead toxicity. Therefore, in this study, we decided to investigate the influence of NAC administration on homocysteine (Hcy) levels, oxidative damage to proteins, and the levels of iron (Fe), transferrin (TRF), and haptoglobin (HPG) in lead (Pb)-exposed workers. The examined population (n = 171) was composed of male employees who worked with Pb. They were randomized into four groups. Workers who were not administered any antioxidants, drugs, vitamins, or dietary supplements were classified as the reference group (n = 49). The remaining three groups consisted of workers who were treated orally with NAC at three different doses (1 x 200, 2 x 200, or 2 x 400 mg) for 12 weeks. After the treatment, blood Pb levels significantly decreased in the groups receiving NAC compared with the reference group. The protein concentration was not affected by NAC administration. In contrast, Hcy levels significantly decreased or showed a strong tendency toward lower values depending on the NAC dose. Levels of the protein carbonyl groups were significantly decreased in all of the groups receiving NAC. Conversely, glutamate dehydrogenase activity was significantly elevated in all of the groups receiving NAC, while the level of protein thiol groups was significantly elevated only in the group receiving 200 mg of NAC. Treatment with NAC did not significantly affect Fe and TRF levels, whereas HPG levels showed a tendency toward lower values. Treatment with NAC normalized the level of Hcy and decreased oxidative stress as measured by the protein carbonyl content; this effect occurred in a dose-dependent manner. Moreover, small doses of NAC elevated the levels of protein thiol groups. Therefore, NAC could be introduced as an alternative therapy for chronic Pb toxicity in humans.
To evaluate the effects of dietary high molybdenum (HMo) and low copper (LCu) concentrations on reproductive toxicity of male mice, 80 mice were divided into 4 groups of 20. These groups were fed with the following: (1) normal control (NC) diet (NC group); (2) NC and HMo diets (HMo group); (3) LCu diet (LCu group); and (4) HMo and LCu diets (HMoLCu group). On the 50th and 100th day, superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) were analyzed to determine oxidative stress states. Morphological changes in testicular tissue were evaluated with hematoxylin and eosin staining and ultrastructural changes were monitored by transmission electron microscopy. The results showed that administration of HMo, LCu, and HMoLCu not only decreased sperm density and motility but also increased the rate of teratosperm occurrence. A significant increase in MDA content and a decrease in SOD, GSH-Px, and T-AOC contents were observed in LCu, HMo, and HMoLCu groups. Testicular tissues and cells of mice were damaged by HMo and the damages were more serious in the case of Cu deficiency. Exposure to HMo adversely affected the reproductive system of male mice, and dietary LCu plays key roles in HMo-induced reproductive toxicity.
1,2-Dichloropropane (1,2-DCP), a solvent, which is the main component of the cleaner used in the offset printing companies in Japan, is suspected to be the causative agent of bile duct cancer, which has been recently reported at high incidence in those offset printing workplaces. While there are some reports about the acute toxicity of 1,2-DCP, no information about its metabolism related to toxicity in animals is available. As part of our efforts toward clarifying the role of 1,2-DCP in the development of cancer, we studied the metabolic pathways and the hepatotoxic effect of 1,2-DCP in mice with or without cytochrome P450 2E1 (CYP2E1) activity. In an in vitro reaction system containing liver homogenate, 1,2-DCP was only metabolized by liver tissue of wild-type mice but not by that of cyp2e1-null mice. Furthermore, the kinetics of the solvent in mice revealed a great difference between the two genotypes; 1,2-DCP administration resulted in dose-dependent hepatic damage, as shown biochemically and pathologically, but this effect was only observed in wild-type mice. The nuclear factor B p52 pathway was involved in the liver response to 1,2-DCP. Our results clearly indicate that the oxidative metabolism of 1,2-DCP in mice is exclusively catalyzed by CYP2E1, and this step is indispensable for the manifestation of the hepatotoxic effect of the solvent.
In occupational exposures, populations are simultaneously exposed to a mixture of chemicals. We aimed to evaluate DNA damage due to possible carcinogen exposure (phenylhydrazine, ethylene oxide, dichloromethane, and 1,2-dichloroethane) in lymphocytes of pharmaceutical industry workers from the same production line. Population comprised 16 subjects (9 females and 7 males) who were exposed to multiple chemicals for 8 months. Genome damage was assessed using alkaline comet assay, micronucleus assay, and comet assay coupled with fluorescent in situ hybridization (comet-FISH). After 8 months of exposure, the issue of irregular use of all available personal protective equipment (PPE) came into light. To decrease the risk of exposure, strict use of PPE was enforced. After 8 months of strict PPE use, micronuclei frequency and comet assay parameters in lymphocytes of pharmaceutical workers significantly decreased compared with prior period of irregular PPE use. Comet-FISH results indicated a significant shift in distribution of signals for the TP 53 gene toward a more frequent occurrence in the comet tail. Prolonged exposure to possible carcinogens may hinder DNA repair mechanisms and affect structural integrity of TP 53. Two indicators of loss of TP 53 gene integrity have risen, namely, TP 53 fragmentation rate in lymphocytes with persistently elevated primary damage and incidence of TP 53 deletions in undamaged lymphocytes.
Frequent and repetitive activities in job and awkward postures are shown as major contributors of musculoskeletal problems in most of the occupational health studies; however, efforts to explore newer risk factor are important to plan interventional measures. In this backdrop, this study examined contribution of fluoride exposure to musculoskeletal complaints. A cross-sectional interviewer-administered questionnaire survey was conducted involving 180 randomly selected subjects from a metal smelting industry. Clinical examination of the subjects was also performed to assess their health status and morbidity details. Assessment of personal exposure to particulate and gaseous fluoride at workplace was conducted. Urinary fluoride level was also examined in post-shift samples collected from study subjects. The mean age of the study subjects was 39.1 (±6.7) years. Majority of the workers (42.5%) were engaged in pot room. About 54% workers were suffering from backache and 66% subjects had joint pain. Exposure of workers to both particulate and gaseous fluoride and post-working shift urinary fluoride level was significantly higher in pot-room workers in comparison with all other workers. It was observed that age (odds ratio (OR): 1.62; 95% confidence interval (CI): 1.18–2.34), drinking untreated water (OR: 1.51; 95% CI: 1.03–2.76), working in pot room (OR: 1.44; 95% CI: 1.13–1.91) and urinary fluoride level (OR: 2.71; 95% CI: 1.81–3.75) had significant effects on musculoskeletal complaints. This study concludes that along with other predictors such as nature of work, posture at work and age of worker, exposure to fluoride also has significant role in the occurrence of musculoskeletal morbidity.
This study was carried out to determine the effects of formaldehyde (FA) inhalation on the humoral immunity of rats and the protective effect of Nigella sativa (NS) oil.
The rats (n = 33) were divided into five groups, with five animals in the control group (FA-free air) and seven in the other four groups. Group FA1 was exposed to FA (5 ppm), group FA + NS1 was treated with NS and exposed to FA (5 ppm), group FA2 was exposed to FA (10 ppm), and group FA + NS2 was treated with NS and exposed to FA (10 ppm). At the end of a 4-week study period, blood samples were collected. Enzyme-linked immunosorbent assay was used to determine the levels of serum total immunoglobulin A (IgA), total immunoglobulin M (IgM), total immunoglobulin G (IgG), and complement 3 (C3).
FA inhalation significantly increased serum IgA, IgM, and C3 levels and decreased serum IgG levels compared with the control group. NS administration decreased serum IgA, IgM, and C3 levels, which were induced by FA inhalation.
FA inhalation significantly increased acute antibody responses and C3 levels in a dose-dependent manner compared with the control group. FA inhalation decreased the secondary immune response compared with the control group. Levels of acute antibody responses and complement following exposure to FA inhalation returned to normal following treatment with NS (immunoregulatory effect). However, NS did not affect the secondary immune response.
This study is aimed at evaluating the association between occupational exposure to organophosphate (OP) and carbamate (CB) pesticides and semen quality as well as levels of reproductive and thyroid hormones of pesticide sprayers in Malihabad, Lucknow, Uttar Pradesh, India. Thirty-five healthy men (unexposed group) and 64 male pesticide sprayers (exposed group) were recruited for clinical evaluation of fertility status. Fresh semen samples were evaluated for sperm quality and analyzed for DNA fragmentation index (DFI) by flow cytometry. Pesticide exposure was assessed by measuring erythrocyte acetylcholinesterase and plasma butyrylcholinesterase (BuChE) with a Test-mate ChE field kit. Serum levels of total testosterone (Tt), prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and free thyroxine (FT4) were analyzed using enzyme immunoassay kits. Evidence of pesticide exposure was found in 88.5% of sprayers and significant increments were observed in sperm DFI with significant decrease in some semen parameters. DFI was negatively correlated with BuChE, sperm concentration, morphology, and vitality in these pesticide sprayers. The levels of Tt, PRL, FT4, and TSH appeared to be normal; however, there was a tendency for increased LH and FSH levels in exposed workers. The results confirm the potential impact of chronic occupational exposure to OP and CB pesticides on male reproductive function, which may cause damage to sperm chromatin, decrease semen quality, and produce alterations in reproductive hormones, leading to adverse reproductive health outcomes.
To investigate the mechanisms of endosulfan-induced reproductive toxicity, the spermatogenic cell lines (GC-1 spg) of mice were treated with 0, 6, 12, and 24 μg/ml endosulfan for 24 h in vitro. The results showed that endosulfan induced apoptosis as well as oxidative stress and mitochondrial dysfunction. Reactive oxygen species and damage of mitochondrial structure were considered as major factors to GC-1 spg cells apoptosis. We further examined the expression of apoptosis-related proteins in mitochondria pathway by Western blot and immunohistochemistry analysis as well as activities. The results showed that endosulfan significantly improved the expressions of cytochrome c and B-cell lymphoma 2 (Bcl-2)-associated X protein and increased the activities of caspases 9 and 3 as well as the downregulation of the expression of Bcl-2 in GC-1 spg cells. The results suggested that exposure to endosulfan might induce the apoptosis of spermatogenic cells via mitochondria-dependent pathway mediated by oxidative stress resulting in the damage of mitochondrial structure and mitochondrial dysfunction.
Lichens can be used as a novel bioresource for natural antioxidants. However, there is need for further investigations to validate the lichens used in medicinal remedies. In this study, the effects of Cetraria islandica and Pseudevernia furfuracae lichen species in streptozotocin (STZ)-induced diabetes were evaluated. Diabetic rats were treated with aqueous lichen extracts (250 and 500 mg/kg/day) for 2 weeks starting at 72 h after STZ injection. On the 14th day, animals were anesthetized, and then metabolic and biochemical parameters were evaluated between control and treatment groups. Pancreatic histology and β-cell mass were examined by hematoxylin and eosin and insulin immunohistochemistry stainings. Our findings revealed that these lichen species could be used safely in this dose range. In addition, C. islandica extracts showed prominent results compared to the doses of P. furfuracae extract for antioxidant capacity. However, the protectivity of C. islandica extract was inadequate against diabetes-induced pancreatic damages via forming oxidative stress. In conclusion, the usage of C. islandica might serve for early intervening in the risk reduction of type 1 diabetes.
The aim of this study was to investigate the effect of oral cadmium (Cd) intoxication on the antioxidant response and its relationship with essential bioelements like copper (Cu) and zinc (Zn). The experimental group was chronically exposed to Cd daily for 8 weeks via consumption of water containing 15 ppm cadmium chloride. Cu, Zn, and Cd concentrations and oxidative stress parameters were analyzed in liver, kidney, and heart tissues. Exposure to Cd led to a significant decrease in the activities of superoxide dismutase in all considered samples while a significant increase in the activity of glutathione peroxidase except for the kidney. We found a significant increase in malondialdehyde concentration in the tissues except for heart. Also oral administration of Cd caused a significant reduction of Zn and Cu in the tissues. Our results allow us to hypothesize that higher Cd concentration in the tissues causes oxidative stress by increasing malondialdehyde as a means of altering antioxidant defense system and deterioration of bioelements in rat liver, kidney, and heart. In addition, further studies are needed to explain the effect of long-term, low-dose exposure to Cd on distribution of bioelements and its relationship with oxidative stress.
The aim of this work was to study whether the increase in antioxidant defenses associated with orchiectomy may account for the reduced susceptibility to aluminum (Al) in male kidney and also to examine whether the reduced antioxidant defenses are associated with androgen levels in orchiectomized (ORX) rats treated with testosterone propionate (TP). Rats were divided into nine groups, namely, intact males (without treatment, treated with sodium lactate, and treated with Al), sham males, ORX males (without treatment, treated with sodium lactate, treated with TP, treated with Al, and treated with TP and Al). Al groups were chronically treated with aluminum lactate for 12 weeks (0.575 mg Al/100 g of body weight, intraperitoneally, three times per week). We reported that ORX rats treated with Al had significantly less lipid peroxidation and an increased level of reduced glutathione (GSH) and GSH/oxidized glutathione ratio in the kidney when compared with intact and TP-treated ORX rats. The activity of superoxide dismutase, catalase, and glutathione peroxidase in ORX rats was much greater than in intact or TP-administered ORX rats. Castration reduced the glomerular alterations caused by Al as well as the number of necrotic tubular cells and nuclear abnormalities. However, we observed a slight alteration in brush border, dilation of proximal tubules, mononuclear infiltrates, and interstitial fibrosis. Castrated males treated with TP showed that this intervention cancels the protective effect of the ORX. This finding suggests that androgens contribute to the development of renal alterations and proteinuria in rats treated with Al. Our results showed that ORX rats are protected against the induction of oxidative stress by Al, but the morphological damage to the kidney tissue induced by the cation was only reduced. Male intact rats treated with Al had more severe glomerulosclerosis, tubular damage, and proteinuria than ORX rats.
This study was undertaken to appreciate genotoxic potential of fipronil herbicides in the roots of Vicia faba seedlings. Fipronil was clearly dose dependent on root growth inhibitors, total soluble protein, and random amplified polymorphic DNA (RAPD) assays. Increase in concentration of fipronil resulted in decreased amount of root length and increased level of protein. For the RAPD analyses, 15 RAPD primers were found to produce unique polymorphic band patterns and were subsequently used to produce a total of 110 bands of 45–1250 bp. Each primer generated 4–11 RAPD bands across 15 primers. The changes occurring in RAPD profiles following fipronil treatment included variation becoming evident as disappearance and/or appearance of DNA bands compared with the normal seedlings. These results indicated that genomic template stability was significantly affected at the above fipronil concentration. This study further confirmed that the RAPD assays are useful in determining potential genotoxicity of fipronil.
Dibromoacetonitrile (DBAN) is a disinfection by-product classified as a potential human and animal carcinogen. This study aimed at investigating the ability of myeloperoxidase (MPO) to oxidize DBAN to cyanide (CN–) in vitro. Detection of CN– served as a marker for the possible generation of free radical intermediates implicated in DBAN-induced toxicity. Optimum conditions for the oxidation of DBAN to CN– were characterized with respect to pH, temperature, and time of incubation as well as DBAN, MPO, potassium chloride, and hydrogen peroxide (H2O2) concentrations in incubation mixtures. Maximum reaction velocity and Michaelis–Menten constant were assessed. Addition of sodium hypochlorite to the reaction mixtures significantly enhanced the rate of the reaction. Addition of the MPO inhibitors, sodium azide, 4-amino benzoic acid hydrazine, or indomethacin to the reaction mixtures significantly decreased the rate of DBAN oxidation. Inclusion of the antioxidant enzyme superoxide dismutase in the incubation mixtures significantly decreased the rate of reaction. Inclusion of the sulfhydryl compounds as reduced glutathione, N-acetylcysteine,
Boerhavia procumbens is traditionally used in the treatment of various disorders including jaundice and gonorrhea, is a refrigerant, and exhibits anti-inflammatory and antispasmodic activities. The purpose of this study was to determine the phytochemical classes, antioxidant and anti-inflammatory activities of methanol extract (BPME) and different fractions (n-hexane (BPHE), ethyl acetate (BPEE), n-butanol (BPBE), and residual aqueous fraction (BPAE)) of B. procumbens against carrageenan-induced paw edema in rats. To assess the anti-inflammatory effects of B. procumbens, 42 Sprague Dawley male rats (150–200 g) were randomly divided into seven groups. Group I received distilled water and group II was treated with diclofenac potassium (10 mg/kg) body weight (bw) orally. Groups III, IV, V, VI, and VII were administered BPME, BPHE, BPEE, BPBE, and BPAE (200 mg/kg bw) orally, 1 h before the treatment with carrageenan (10 mg/kg bw) in rats. Anti-inflammatory effects of B. procumbens were determined by estimating the inhibition of edema at 1st, 2nd, and 3rd hour after carrageenan injection. Qualitative analysis of methanol extract indicated the composition of diverse classes, namely, flavonoids, tannins, saponins, phlobatannins, cardiac glycosides, alkaloids, terpenoids, and anthraquinones. Quantitative determination illustrated that BPBE and BPEE possessed the highest concentration of total phenolic (60.45 ± 2.1 mg gallic acid equivalent per gram sample) and total flavonoid content (68.05 ± 2.3 mg rutin equivalent per gram sample), respectively. A dose-dependent response for antioxidant activity was exhibited by all the samples. The sample with the highest aptitude for antioxidant activity was the BPBE for 2,2-azobis,3-ethylbenzothiozoline-6-sulfonic acid radical scavenging and total antioxidant capacity. Carrageenan-induced paw edema was significantly (p < 0.05) inhibited by BPBE and BPME at the 1st, 2nd, and 3rd hour and was comparable to control drug diclofenac potassium. Results revealed that various fractions of B. procumbens manifested the antioxidant and anti-inflammatory potential and accredit the local use of B. procumbens in various disorders.
This study aims to evaluate the protective effect of grape seed proanthocyanidin extract (GSPE) on cadmium (Cd)-induced testicular apoptosis, endothelial nitric oxide synthases (eNOS) expression, and toxicity in rats. A total of 24 male Wistar rats were divided into four groups, namely, control, Cd (2.5 mg/kg), Cd + GSPE (100 mg/kg/day), and GSPE. Spermatogenesis and mean seminiferous tubule diameter were significantly decreased in the Cd groups. Furthermore, the GSPE-treated animals showed an improved histological appearance in the Cd group. The immunoreactivity of eNOS and the number of apoptotic cells were increased in Cd group. Our data indicate a significant reduction of terminal deoxynucleotide transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end-labeling staining and a decrease in the expression of eNOS in the testes tissue of the Cd group treated with GSPE therapy. Therefore, our results suggest that GSPE acts as a potent protective agent against Cd-induced testicular toxicity in rats.
Phthalates are abundantly produced plasticizers, and dibutyl phthalate (DBP) is the most widely used derivative in various consumer products and medical devices. This study was conducted to further explore the potential testicular toxicity of DBP in adult rats and to elucidate the underlying mechanisms. Adult male albino rats were treated orally with DBP at doses of 0, 200, 400, or 600 mg/kg/day for 15 consecutive days. Testicular weight, sperm count, and motility were significantly decreased. Treatment with DBP decreased serum follicle-stimulating hormone and testosterone levels and testicular lactate dehydrogenase activity. DBP treatment also decreased serum total antioxidant capacity and the activities of the testicular antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione reductase. Further, DBP treatment provoked degeneration with absence of spermatogenesis and sperms and necrosis in some of seminiferous tubules. These results indicated that oxidative stress and subsequent decrease in testosterone secretion were the potential underlying mechanism of DBP-induced testicular toxicity.
Carbosulfan is often used in agriculture for pest control on crops and for treatment against pyrethroid-resistant mosquitoes. This study investigated the impact of carbosulfan on oxidative stress markers, antioxidant defense, hematological, biochemical, and enzymological parameters in Sprague Dawley rats. Rats were orally administered carbosulfan doses of 1.02 to 10.20 mg/kg body weight daily; after 96 h, blood samples were taken, and the liver, kidney, and brain were dissected out for study. Results indicate that carbosulfan significantly increased the levels of lipid peroxidation and suppressed the activity of reduced glutathione, glutathione reductase, catalase, glucose-6-phosphate dehydrogenase, and adenosine triphosphatase. A mixed trend was observed in the activity of superoxide dismutase, while an increase was observed in the levels of serum uric acid, urea, aspartate aminotransferase, and alanine aminotransferase. Hemoglobin and albumin levels decreased but no significant differences were observed in creatinine and bilirubin levels. Future studies should include a more detailed analysis of the effects of chronic carbosulfan exposure on these biomarkers to further assess the impact of the pesticide on mammalian models.
In this study, the association between heavy metals in water and cyprinids sampled from the Yeşilırmak River stretch, which is frequently exposed to pollutant sources (a sugar production factory (Turhal) and solid wastes dump area (Taşlıçiftlik) was explored, and the oxidative effects of heavy metals on cyprinids were evaluated through analyzing some liver enzymes, namely, superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and cortisol. The heavy metal concentrations of both fish and water, collected from three different locations along the river during the summer of 2011 and winter of 2010 (Turhal, Taşlıçiftlik, and Gümenek), were determined by inductively coupled plasma atomic emission spectroscopy (ICP-AES). The water and fish liver heavy metal concentrations exhibited increasing trends from upstream (Gümenek) to downstream (Turhal). The water and liver samples collected during the summer had higher heavy metal concentrations than those obtained during the winter. The mean heavy metal concentrations increased from Gümenek to Turhal. The liver heavy metal concentrations were higher than those in the water and exhibited almost the same increasing trend from Gümenek to Turhal. Positive relationships between liver and water heavy metal concentrations, especially for cadmium (R 2 = 0.91) and lead (R 2 = 0.98), were obtained. Among the liver enzymes, only MDA followed the same increasing trend from Gümenek to Turhal as was obtained for heavy metals. On the other hand, CAT and SOD had a contrary spatial pattern of change to those of heavy metals and MDA. Although the values of heavy metals and MDA in Taşlıçiftlik were between the two other locations, fish inhabiting this locality had significantly higher values of cortisol, which is an indication of the other stress-causing factors for fish.
Crystalline silica (SiO2) is an important material for industry but is considered potentially carcinogenic. Inhalation of a crystalline SiO2 aerosol may contribute to serious lung diseases. Crystalline SiO2 particles are commonly used as a positive control in toxicity assays of particulate materials (e.g. nanoparticles). Crystalline SiO2 induces oxidative stress resulting in lipid peroxidation, but the acute oxidative stress response in the lung is not well understood. Lipid peroxidation during the acute stage of oxidative stress after instillation of crystalline SiO2 into rats was examined by bronchoalveolar lavage fluid (BALF) analysis. The levels of 8-iso-prostaglandin F2α and hydroxyoctadecadienoic acid (HODE) in the BALF were measured using liquid chromatography coupled to quadrupole mass spectrometry. The concentration of the antioxidant protein heme oxygenase-1 (HO-1) in the BALF was determined using enzyme-linked immunosorbent assay. Intratracheal instillation of crystalline SiO2 increased the level of HODE and HO-1 in BALF at 24 h after administration. The levels of HODE and HO-1 returned to baseline at 72 h after instillation. Lactate dehydrogenase leakage was observed only after 1 h instillation. These results suggest that the contribution of oxidative stress to the pulmonary toxicity of crystalline SiO2 is minimal in the early acute stage after exposure.
Several chemicals such as N-diethylnitrosamine (DEN) promote hepatocellular cancer in rodents and induce hepatocyte injury. DEN affects the initiation stage of carcinogenesis together with enhanced cell proliferation accompanied by hepatocellular necrosis. DEN-induced hepatocellular necrosis is reported to be related to enhanced generation of reactive oxygen species. Carnosine (CAR), taurine (TAU), and betaine (BET) are known to have powerful antioxidant properties. We aimed to investigate the effects of CAR, TAU, and BET pretreatments on DEN-induced oxidative stress and liver injury in male rats. Rats were given CAR (2 g L–1 in drinking water), TAU (2.5% in chow), and BET (2.5% in chow) for 6 weeks and DEN (200 mg kg–1 intraperitoneally) was given 2 days before the end of this period. Serum alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and -glutamyl transferase activities were determined and a histopathologic evaluation was performed on the liver tissue. Oxidative stress was detected in the liver by measuring malondialdehyde, diene conjugate, protein carbonyl and nitrotyrosine levels, glutathione and glutathione peroxidase levels, and superoxide dismutase and glutathione transferase activities. Pretreatments with CAR, TAU, and BET decreased liver prooxidant status without remarkable changes in antioxidant parameters in DEN-treated rats. Pretreatments with TAU and BET, but not CAR, were also found to be effective to reduce liver damage in DEN-treated rats. In conclusion, TAU, BET, and possibly CAR may have an ameliorating effect on DEN-induced hepatic injury by reducing oxidative stress in rats.
Lithium titanate (Li2TiO3) nanoparticles (LTT NPs; <100 nm) are widely used in battery technology, porcelain enamels, and ceramic insulating bodies. With the increased applications of LTT NPs, the concerns about their potential human toxicity effects and their environmental impact were also increased. However, toxicity data for LTT NPs relating to human health are very limited. Therefore, the purpose of this study was to evaluate whether LTT NPs are able to induce genetic damage in human peripheral lymphocytes in vitro when taking into consideration that DNA damage plays an important role in carcinogenesis. With this aim, the chromosome aberrations (CA), sister chromatid exchanges (SCE), and micronucleus (MN) assays were used as genotoxicity end points. Human peripheral lymphocytes obtained from five healthy male volunteers were exposed to LTT NPs at final dispersed concentrations ranging from 0 to 1000 μg/mL for 72 h at 37°C. The obtained results indicated that LTT NPs compound did not induce DNA damage in human peripheral lymphocytes as depicted by CA/cell, SCE/cell, and MN/1000 cell values in all concentrations tested. In summary, our results revealed that exposure to LTT NPs is not capable of inducing DNA lesions in human peripheral lymphocytes for the first time.
The nitrophenols (NPs) are water-soluble compounds. These compounds pose a significant health threat since they are priority environmental pollutants. In this study, 2-Nitrophenol (2NP) and 2,4-dinitrophenol (DNP) were examined for embryo and early life stage toxicity in zebrafish (Danio rerio). Acute toxicity and teratogenicity of 2NP and DNP were tested for 4 days using zebrafish embryos. The typical lesions observed were no somite formation, incomplete eye and head development, tail curvature, weak pigmentation (≤48 hours postfertilization (hpf)), kyphosis, scoliosis, yolk sac deformity, and nonpigmentation (72 hpf). Also, embryo and larval mortality increased and hatching success decreased. The severity of abnormalities and mortalities were concentration- and compound-dependent. Of the compounds tested, 2,4-DNP was found to be highly toxic to the fish embryos following exposure. The median lethal concentrations and median effective concentrations for 2NP are 18.7 mg/L and 7.9 mg/L, respectively; the corresponding values for DNP are 9.65 mg/L and 3.05 mg/L for 48 h. The chorda deformity was the most sensitive endpoint measured. It is suggested that the embryotoxicity may be mediated by an oxidative phosphorylation uncoupling mechanism. This article is the first to describe the teratogenicity and embryotoxicity of two NPs to the early life stages of zebrafish.
Rhododendron arboreum Smith. (Ericaceae), an evergreen small tree, is one of the 1000 species that belongs to genus Rhododendron distributed worldwide. In folk medicine, as various parts of this plant exhibit medicinal properties, it is used in the treatment of different ailments. The present study was designed to evaluate the potential anti-inflammatory and antinociceptive effects of methanolic extract of R. arboreum bark, followed by activity-guided fractionation of n-hexane, n-butanol, chloroform, ethyl acetate and aqueous fractions. The ethyl acetate fraction (200 mg/kg i.p.) showed the maximum analgesic effect (82%) in acetic acid-induced writhing, followed, to a less extent, by crude extract and chloroform fraction both at a dose of 200 mg/kg i.p. (65.09% and 67.89%, respectively). In carrageenan-induced mouse paw oedema, the crude extract and its related fractions displayed in a dose-dependent manner (50–200 mg/kg i.p.) an anti-inflammatory activity for all time-courses (1–5 hrs). For the active extract/fractions (200 mg/kg i.p.), the maximum effect was observed 5 h after carrageenan injection. These evidences were also supported by in vitro lipoxygenase inhibitory properties. In conclusion, R. arboreum crude methanolic extract and its fractions exhibited anti-inflammatory and antinociceptive effects. For these reasons, this plant could be a promising source of new compounds for the management of pain and inflammatory diseases.
Bisphenol A (BPA) is a commonly used material in daily life, and it is argued to cause oxidative stress in liver and ovarian tissue. α-Lipoic acid (ALA) and α-tocopherol (ATF), two of the most effective antioxidants, may play a role in preventing the toxic effect. Therefore, the purpose of this study was to examine the beneficial effects of ALA, ATF, and that of ALA + ATF combination on oxidative damage induced by BPA. Female Wistar rats were divided into five groups (control, BPA, BPA + ALA, BPA + ATF, and BPA + ALA + ATF). BPA (25 mg/kg/day), ALA (100 mg/kg/day), and ATF (20 mg/kg/day) were administered for 30 days. The levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), liver malondialdehyde (L-MDA) and glutathione peroxidase (L-GPx), and ovarian malondialdehyde (Ov-MDA) and nitric oxide (Ov-NO) were significantly higher in the BPA-treated groups compared with the control group. The levels of AST and ALT decreased in the BPA + ALA, BPA + ATF, and BPA + ALA + ATF groups compared with the BPA group. Similarly, BPA + ALA or BPA + ATF led to decreases in L-MDA and Ov-MDA levels compared with the BPA group. However, the BPA + ALA + ATF group showed a significant decrease in L-MDA levels compared with the BPA + ALA group and the BPA + ATF group. The levels of L-GPx decreased in the BPA + ATF and the BPA + ALA + ATF groups compared with the BPA group. The administration of ATF and ALA + ATF significantly decreased the Ov-NO levels. This study demonstrates that BPA causes oxidative damage in liver and ovarian tissues. ALA, ATF, or their combination were found to be beneficial in preventing BPA-induced oxidative stress.
Silver (Ag) and gold nanoparticles (Au NPs) have wide applications. They are increasingly being used in the medical devices, biosensors, cancer cell imaging, and cosmetics. Increased applications of these NPs in the technological advances have also led to the risk of exposure to these particles. This study investigated the toxic effects of Ag and Au NPs (1 μM and 2 μM, oral) on mouse erythrocytes and tissues after 14 consecutive days’ exposure. Our results demonstrate significant increase in reactive oxygen species (ROS) and depletion of antioxidant enzyme status in erythrocytes and tissues. Hepatic and renal toxicity was evident from liver and kidney function tests. Inflammatory markers, interleukin-6 and nitric oxide synthase increased in plasma on administration following exposure to these NPs at both the doses. A more pronounced increase was noted in kidney metallothionein (MT) compared to liver MT on exposure to these NPs. Toxic potential of these NPs was further confirmed by increased 8-hydroxy-2'-deoxyguanosine levels in urine, a biomarker of DNA damage. Among the two NPs, Ag NP was more toxic at 2 μM dose compared to lower dose of 1 μM. The study suggests oxidative stress as the major mechanism responsible for the toxic manifestations induced by Ag and Au NPs.
The hsp70 and hsp90 expression patterns and catalase (CAT) activity in the freshwater planaria Dugesia japonica exposed to cadmium (Cd) under laboratory conditions were investigated. Planaria were exposed to a range of Cd concentrations (0–150 μg Cd/L) for 24 h. The expression levels of hsp70 and hsp90 were determined by relative quantitative real-time polymerase chain reaction. Within the overall dose range in the experiment, the expression level of hsp70 and the activity of CAT in D. japonica were altered significantly. Hsp70 was induced in D. japonica upon Cd exposure concentrations as low as 9.375 μg Cd/L. No significant effect on the expression level of hsp90 was observed. Our findings demonstrated that stress gene hsp70, but not hsp90, was responsive to Cd contamination in D. japonica. CAT activity was significantly induced at concentrations of 18.75, 37.5, and 75 μg Cd/L after 24-h exposure. We recommend that the use of hsp70 as a biomarker should be complemented by evidence of changes in other parameters, such as CAT activity, in D. japonica.
This study aims to evaluate the possible ameliorative effect of earthworm (Allolobophora caliginosa) extract (EE) against silicon dioxide nanoparticles (SiNPs)-induced liver injury in male albino rats. The effectiveness of EE was compared with silymarin as a standard hepatoprotective drug. The present work demonstrates the antioxidant activity of EE by 1,1-diphenyl-2-picrylhydrazyl assay. Administration of SiNPs, for 15 consecutive days, caused changes in most of the biochemical parameters, namely, serum aminotransferase enzymes activities (alanine transaminase and aspartate transaminase), alkaline phosphatase activity, total protein, total and direct bilirubin level, malondialdehyde, glutathione reduced, catalase, superoxide dismutase, glutathione reductase, and glutathione peroxidase. In addition, administration of SiNPs induced changes in liver tissue architecture. Administration of EE, for subsequent 30 days, to SiNPs exposure demonstrated significant ameliorative effects on nearly all the studied parameters, and such effects were compatible with those of silymarin. In addition, the administration of EE repairs, to some extent, the abnormal architecture of the liver tissue induced by SiNPs.
Epidemiological reports have indicated a correlation between the increasing bisphenol A (BPA) levels in the environment and the incidence of male infertility. In this study, the protective effects of melatonin on BPA-induced oxidative stress and apoptosis were investigated in the rat testes and epididymal sperm. Melatonin (10 mg/kg body weight (bw)) was injected concurrently with BPA (50 mg/kg bw) for 3 and 6 weeks. The administration of BPA significantly increased oxidative stress in the testes and epididymal sperm. This was associated with a decrease in the serum testosterone level as well as sperm quality, chromatin condensation/de-condensation level, and the percentage of haploid germ cells in the semen. BPA administration caused a significant increase in apoptosis accompanied by a decrease in the expression of the antiapoptotic proteins Bcl-2 in the testes and epididymal sperm. The concurrent administration of melatonin decreased oxidative stress by modulating the levels of glutathione, superoxide dismutase, and catalase as well as the malondialdehyde and hydrogen peroxide concentrations in the testes and sperm. Melatonin sustained Bcl-2 expression and controlled apoptosis. Furthermore, melatonin maintained the testosterone levels, ameliorated histopathological changes, increased the percentages of seminal haploid germ cells, and protected sperm chromatin condensation process, indicating appropriate spermatogenesis with production of functional sperm. In conclusion, melatonin protected against BPA-induced apoptosis by controlling Bcl-2 expression and ameliorating oxidative stress in the testes and sperm. Thus, melatonin is a promising pharmacological agent for preventing the potential reproductive toxicity of BPA following occupational or environmental exposures.
Sulfur mustard (SM), a bifunctional alkylating agent that causes severe lung damage, is a significant threat to both military and civilian populations. The mechanisms mediating the cytotoxic effects of SM are unknown and were investigated in this study. The purpose of this study was to establish a rat model of SM-induced lung injury to observe the resulting changes in the lungs. Male rats (Sprague Dawley) were anesthetized, intratracheally intubated, and exposed to 2 mg/kg of SM by intratracheal instillation. Animals were euthanized 6, 24, 48, and 72 h post-exposure, and bronchoalveolar lavage fluid (BALF) and lung tissues were collected. Exposure of rats to SM resulted in rapid pulmonary toxicity, including partial bronchiolar epithelium cell shedding, focal ulceration, and an increased amount of inflammatory exudate and number of cells in the alveoli. There was also evidence that the protein content and cell count of BALF peaked at 48 h, and the alveolar septum was widened and filled with lymphocytes. SM exposure also resulted in partial loss of type I alveolar epithelial cell membranes, fuzzy mitochondrial cristae, detachment and dissociation of ribosomes attached to the surface of rough endoplasmic reticulum, cracked, missing, and disorganized microvilli of type II alveolar epithelial cells, and increased apoptotic cells in the alveolar septum. The propylene glycol control group, however, was the same as the normal group. These data demonstrate that the mechanism of a high concentration of SM (2 mg/kg) induced acute lung injury include histologic changes, inflammatory reactions, apoptosis, oxidative stress, and nuclear DNA damage; the degree of injury is time dependent.
The aim of this study was to investigate the effects of taurine (TA) on serum lipid profiles following chronic coadministration of chlorpyrifos (CP) and lead acetate (Pb) in male Wistar rats. Fifty rats randomly distributed into five groups served as subjects. Distilled water (DW) was given to DW group, while soya oil (SO; 1 mL kg–1) was given to SO group. The TA group was treated with TA (50 mg kg–1). The CP + Pb group was administered sequentially with CP (4.25 mg kg–1; 1/20th median lethal dose (LD50)) and Pb at 233.25 mg kg–1 (1/20th LD50), while the TA + CP + Pb group received TA (50 mg kg–1), CP (4.25 mg kg–1), and Pb (233.25 mg kg–1) sequentially. The treatments were administered once daily by oral gavage for 16 weeks. The rats were euthanised, and the blood samples were collected at the termination of the study. Sera obtained from the blood samples were analyzed for total cholesterol, high-density lipoprotein cholesterol, triglycerides, and malondialdehyde, and also the activities of serum antioxidant enzymes including superoxide dismutase, catalase and glutathione peroxidase were analyzed. The low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, and atherogenic index were calculated. The results showed that CP and Pb induced alterations in the serum lipid profiles and evoked oxidative stress. TA alleviated the disruptions in the serum lipid profiles of the rats partially by mitigating oxidative stress. It was concluded that TA may be used for prophylaxis against serum lipid disorders in animals that were constantly co-exposed to CP and Pb in the environment.
Three hundred and eight samples of rice purchased from retail markets in six different provinces in Iran from March 2012 to January 2013 were surveyed for the presence of ochratoxin A (OTA) using enzyme-linked immunosorbent assay. The recovery percentages of OTA from spiked rice samples at concentrations of 5 and 10 ng/g were found to be 85.3% and 86.7%, respectively. Analytical results showed a 9.4% frequency of contamination from total analyzed rice samples with a mean OTA level of 3.60 ± 2.66 ng/g. Concentrations of OTA in positive samples ranged from 0.84 ng/g to 11.37 ng/g, and in 17.3% of contaminated rice samples the concentrations exceeded the maximum tolerance limit set by European regulations for OTA in cereals (5 ng/g). Based on the results of this study, the estimated daily intake of OTA in rice was 0.62 ng/kg body weight/day for Iranian consumers.
It has been reported by the Ministry of Environment in Kosova that particle emissions from one of the units of the coal-fired power plants (Kosova A) in Kastriot/Obiliq were exceeding the European standard by some 74 times. Besides the particle emission, there is also release of sulphur dioxide, mono-nitrogen oxide (NOx), carbon monoxide, carbon dioxide, organic compounds and heavy metals. In addition, there is also release of heavy metals and organic compounds from a nearby solid waste dumpsite. Together, they are considered to be responsible for the increased health problems of the population living in the vicinity.To study the genetic effects of these emissions we focused on the genetic load, that is, recessive mutations that affect the fitness of their carriers, of exposed wild living Drosophila melanogaster. The effects of ash from the dumpsite on the other hand were investigated upon feeding the ash with the nutrient medium. Our results revealed that the D. melanogaster population from the Kastriot/Obiliq area carries a high genetic load of 54.7%. Drosophila fed with the nutrient medium containing ash in a concentration of 1% carried a genetic load of 37.1%, whilst increasing concentrations (2% and 3% of ash) led to higher genetic loads of 68.7% and 67.4%, respectively.
Carbon monoxide (CO) is a major constituent of traffic-related air pollution and is also produced endogenously under conditions of oxygen-mediated stress. It has been shown to affect both oxidative stress and inflammation. However, its role in lipid metabolism has been neglected. Using short exposure times, the effect of CO on J774A.1 macrophage atherogenic functions was investigated up to 16 h after exposure. Exposure of macrophages was found to be pro-atherogenic as it significantly increased triglyceride mass, up to 60%, and decreased high-density lipoprotein-mediated cholesterol efflux, up to 27%. In contrast, paraoxonase 2 lactonase activity was increased, up to 65%, and cellular oxidative stress was attenuated by 29%, compared with the control cells. The above results on lipid metabolism may lead to arterial macrophage foam cell formation, the hallmark of early atherogenesis.
In this study, concentrations of mercury (Hg) were analyzed in some marine biota species (fish, shrimp, and crab) from Khuzestan shore, north part of the Persian Gulf. It was also our intention to evaluate potential risks to human health associated with seafood consumption. The results indicated that concentrations of Hg in the fish and crustacean were different among the species and tissues. Liver in fish and hepatopancreas in crustacean exhibited higher Hg concentration than the other tissues. The highest concentration of Hg was detected in Acanthopagrus latus liver (1.37 µg/g), followed by Labeo rohita (0.87 µg/g), Johnius belangerii (0.79 µg/g), and Barbus grypus (0.69 µg/g), respectively. Also the highest Hg concentrations were detected in shrimp species, Penaeus semisulcatus hepatopancreas (0.95 µg/g), followed by blue crab Portunus pelagicus (0.76 µg/g) and Metapenaues affinis (0.64 µg/g), respectively. The comparison indicated that benthic species were more contaminated than were other pelagic species. The results indicated that highest concentrations of Hg between different stations were detected in Musa estuary. The Hg concentration in all species were low than standards, expect in A. latus and P. semisulcatus collected from Musa estuary (S4). The variation in Hg levels among the species is likely to have resulted from metal bioavailability, changes in tissue composition, habitat,s and locations.
Carbon nanotubes with extraordinary properties may become a novel drug and gene delivery tool in nanomedicine; however, insufficient information is available regarding their biosafety. Therefore, this work was performed to study the effect of prenatal exposure of single-walled carbon nanotubes (SWCNTs) on reproductive and neurobehavioral endpoints in mice. Thirty pregnant female mice were assigned to three groups (n = 10 for each group). The two treated groups were injected intraperitoneally (i.p.) with 1 or 10 mg/kg body weight (b.w.) of SWCNTs suspended in 1 ml of phosphate buffer saline (PBS) on gestational days 0 and 3. The control group was injected i.p. with an equal volume of PBS. The neurobehavioral ontogeny of pups was evaluated using a modified Fox battery. A decrease in litter size on postnatal day 2 was observed in the group treated with 10 mg/kg b.w. of SWCNTs whereas no significant differences between groups were observed in any other parameters. The behavioral development of pups did not show significant differences during growth except for the surface righting reflex, which showed significant delay compared to control in the group treated with 1 mg/kg b.w. SWCNTs. Moreover, exposed offspring (10 mg/kg b.w. SWCNTs) displayed enhanced anxiety in the elevated plus maze; however, other ethological analysis (Morris water maze and open field test) did not show behavioral changes in the experimental groups. In conclusion, the present results demonstrated small changes in offspring sensory and motor development following exposure to SWCNTs and support the idea that SWCNT risk assessment merits further investigation.
The protective effect of quercetin (QT) on atrazine (ATZ)-induced testicular damage in rats was investigated. Sexually mature male Wistar rats (weighing 220–250 g) divided into four groups with six animals in each group were given ATZ (120 mg kg–1; 1/16 of the median lethal dose for an oral dose) and/or QT (10 mg kg–1) daily via gavage for 16 days. By the end of day 16, rats given ATZ alone had significantly lower sperm counts, daily spermatozoa production, and sperm motility and significantly higher abnormal sperm numbers than the untreated control rats. The rats given ATZ alone also had significantly decreased 3β-hydroxtsteroid dehydrogenase (HSD) and 17β-HSD activities than the control rats. Lactate dehydrogenase activity and malondialdehyde levels were significantly increased, whereas superoxide dismutase activity decreased but glutathione levels remain unaffected after ATZ exposure. These changes were reversed toward control values in the QT + ATZ-treated animals, though the sperm motility was 28% below the control levels but was still higher than in the ATZ-treated rats. The results indicate that QT might improve testicular function of rats exposed to ATZ, but its protective effect on sperm motility might be partial.
Nickel compounds are an important class of environmental pollutants and carcinogens. Chronic exposure to nickel compounds has been connected with increased risks of numerous cancers, including lung and kidney cancers. But the precise mechanism by which nickel compounds exert their carcinogenic properties is not completely understood. In this study, kidney cancer cells namely human embryonic kidney 293-containing SV40 large T-antigen (HEK293T) and 786-0 were incubated with various concentrations of nickel chloride for 24 h before analysing the expression of three histone H3K27 methylation-modifying enzymes and H3K27me3 using quantitative real-time polymerase chain reaction, Western blot and immunofluorescence analyses. Our results showed that incubation of nickel chloride upregulated the expression of H3K27me3 demethylase jumonji domain-containing protein 3 (JMJD3) in kidney cancer cells, which was accompanied by the reduction in the protein level of H3K27me3. Enhanced demethylation of H3K27me3 may represent a novel mechanism underlying the carcinogenicity of nickel compounds.
T-2 toxin is a mycotoxin produced by phytopathogenic fungi of the Fusarium genus and has many well-studied deleterious effects on mammalian cells and reproductive tract. Despite the wide scale studies, the effects on preimplantation stage embryos are lacking. The aim of our study was to investigate the impact of T-2 on the cleavage stage of mouse embryos with regard to development to blastocysts and nuclear chromatin status.
Six-weeks-old BDF1 female mice were superovulated and placed together overnight with mature males. Zygotes were flushed 20 h after human chorionic gonadotropin injection and divided randomly into treated (supplemented with 0.5, 0.75, and 1 ng/ml T-2) and nontreated (control) groups. Embryos were cultured in vitro for 96 h. Developmental stage was evaluated in the 72nd- and 96th-h for assessment of development dynamics. At the end of culture period, blastocysts from treated and control groups with normal morphology were selected for nuclear chromatin analysis. Blastocysts were categorized (grade A, B, and C) depending on the proportion of blasomeres with micronuclei and/or lobulated nuclei.
Our data show significant decrease in the proportions of blastocysts in the 0.75 and 1 ng/ml toxin-supplemented groups compared with the control group. Blastocyst rate did not differ in embryos treated with 0.5 ng/ml T-2 but 24 h delay was found in blastocoel formation in all the treated groups. Only grade A (21.1%) and B (78.9%) blastocysts were found in low-toxin-contaminated group similar to the control ones (50–50%). Grade C embryos appeared in the 0.75 ng/ml (10%) treated group and the rate increased significantly (33.3%) in the highest contaminated group.
T-2 mycotoxin has a harmful effect on early embryo development which results in decreased blastocyst proportion, delayed blastulation, and increased rate of chromatin damage.
This study is aimed at elucidating the possible protective effects of Nigella sativa oil (NSO) in alleviating the toxicity of chlorpyrifos (CPF) on reproductive performance in male rats. Animals were orally administered with NSO (1 ml/kg/day), CPF (20 mg/kg/day), and NSO + CPF every day for 4 weeks. Results showed that CPF decreased spermatid number, sperm count, daily sperm production, and sperm motility while increased dead sperm and abnormal sperm compared with the control. Also the levels of testosterone, thyroxine levels, steroidogenic enzyme 17-ketosteroid reductase, body weight, food intake, and relative weight of reproductive organs were decreased. Thiobarbituric acid reactive substances were increased, while glutathione (GSH) and antioxidant enzymes were decreased in plasma and testes of rats treated with CPF. Histopathological examination of testes showed a decrease in the number of seminiferous tubules, form shrinkage, enlargement of the connective tissue and gametogenic changes in germ cells of rats treated with CPF. NSO alone increased testosterone, semen characteristics, GSH, and antioxidant enzymes and decreased the levels of free radicals. Furthermore, the presence of NSO with CPF alleviates its toxic effects. Our results indicated that NSO can improve semen picture and moderate CPF-induced reproductive toxicity.
Hepatic fibrosis, characterized by extracellular matrix accumulation, is the common cause of chronic liver failure and is a leading cause of morbidity and mortality worldwide. The aim of the present study was to evaluate the effect of dried flowers of Woodfordia fruticosa on carbon tetrachloride (CCl4)-induced hepatic fibrosis in rat model. Hepatic fibrosis was induced in male Wistar rats by CCl4 administration (150 μl/100 g rat weight, oral) twice a week for 10 weeks. In preventive model, administration of daily doses of methanolic extract of W. fruticosa (MEWF) at two different doses (100 mg/kg, body weight (b.w.) and 200 mg/kg, b.w.) was started 1 week before the onset of CCl4 administration and continued for 10 weeks. In curative model, MEWF at 100 and 200 mg/kg were given for last 2 weeks after the establishment of fibrosis. MEWF at a dose of 200 mg/kg was able to exert a more pronounced effect as evidenced histologically by significant reduction in fibrotic septa formation in liver tissue, immunohistochemically by abridged expression of collagen III, and also biochemically by serum and tissue antioxidant status, lipid peroxidation, and hydroxyproline level. Liquid chromatography–mass spectrometry analysis revealed the presence of confertin, quercetin methyl ether, ellagic acid, and stigmasterol in MEWF, which could be responsible for its antifibrotic activity. These results indicate the effective protection exerted by MEWF against CCl4-induced hepatic fibrosis in a dose-dependent manner.
The main aim of this study was to biomonitor mercury (Hg), arsenic (As), cadmium (Cd), lead (Pb) and copper (Cu) concentrations in the Arvand River using Heteropnestis fossilis and Parasesarma persicum. Comparison of heavy metals among the stations indicated that the concentrations of Hg, As, Cd, Cu and Pb in sediment samples were apparently different among the stations. The results of linear regression analyses showed that there were significant correlations (p < 0.05) between Hg, As and Pb elements in sediment and hepatopancreas of P. persicum and between As in sediment and liver of H. fossilis. These findings showed that P. persicum could be considered as a biomonitor of Hg, As and Pb and H. fossilis as a biomonitor of As contamination in sediment of the Arvand River.
Research has suggested that natural antioxidant, crocin, an active ingredient of saffron, may protect against diazinon (DZN)-induced toxicity. Although increased production of lipid peroxidation by DZN in rat aorta has been shown previously, the effects of DZN on oxidative stress-induced apoptosis in vascular system have not been evaluated. In this study, the effect of crocin on DZN-induced apoptosis in rat vascular system was investigated. The rats were divided into 7 groups: corn oil (control), DZN (15 mg/kg/day, gavage), crocin (12.5, 25, and 50 mg/kg/day, intraperitoneally (i.p.)) + DZN, vitamin E (200 IU/kg, i.p., 3 days a week) + DZN, and crocin (50 mg/kg/day, i.p.). The treatments were continued for 4 weeks. Levels of apoptotic (Bax, caspase 3, and caspase 9) and antiapoptotic proteins (Bcl2) were analyzed by Western blotting. Transcript levels of Bax and Bcl2 genes were determined using quantitative real-time polymerase chain reaction. Results showed DZN-induced apoptosis by activation of caspase 9 and caspase 3 and by increasing the Bax/Bcl2 ratio (both protein and messenger RNA levels). Crocin and vitamin E inhibited apoptosis induced by DZN. In summary, subchronic exposure to DZN induced caspase-mediated apoptosis, and crocin reduced the toxic effects of DZN by inhibiting apoptosis in aortic tissue.
An increase in enviromental pollution may lead to mercury toxicity of fish origin due to the accumulative nature of methylmercury in fish. The main sources of human exposure to organic mercury compounds are contaminated fish and other seafoods. This descriptive study was planned to determine mercury levels in anchovy and in hair samples from individuals with different fish consumption habits, and to evaluate those individuals in terms of toxic effects. For that purpose, we analyzed 100 anchovies from the Black Sea and 100 anchovies from the Sea of Marmara, and assessed 25 wholesale workers in fish markets and 25 cleaning firm employees from both Ankara and Istanbul. Mercury levels in samples were measured using a cold vapor atomic absorption spectrophotometer. Participants were examined neurologically and mini mental state examination was applied to evaluate their cognitive functions. Mercury levels in fish were found to be below the national and international permitted levels. There was no statistically significant relation between mercury levels and the sea from which fish were caught. Hair mercury levels for all participants were within permitted ranges. However, hair mercury levels in both cities increased significantly with amount and frequency of fish consumption. A significant correlation was determined at correlation analysis between levels of fish consumption and hair mercury levels in the fishmongers and in the entire group (r = 0.32, p = 0.025; r = 0.23, p = 0.023, respectively). Neurological examination results were normal, except for a decrease in deep tendon reflexes in some participants in both cities. There was no correlation between Standardized Mini Mental State Examination results and hair mercury levels. We conclude that establishing a monitoring system for mercury levels in fish and humans will be useful in terms of evaluating potential neurotoxic effects.
Polycyclic aromatic hydrocarbons (PAHs) are potent environmental pollutants. Benzo[α]pyrene (B[α]P) is the major compound of PAHs that acts by activating aryl hydrocarbon receptor (AhR) in cells. B[α]P is a known carcinogen and an immunotoxicant; however, its role with regard to nuclear factor of activated T cell (NFAT) pathway is unclear. AhR and NFAT signaling pathways have common roles in pathological functions in immunotoxicity and lung cancer. In this study, the effect of AhR activation on expression and signaling cross talk of AhR and NFATc1 pathways in mouse lung tissue has been investigated.
Swiss albino mice were randomly allocated to five groups and administered with cyclosporin A (CsA) and B[α]P for seven constitutive days. Animals were then killed, and lung tissues were obtained after washing the whole blood. Paraffin-embedded blocks were prepared, and 5 µm sections were cut for histopathological and immunohistochemical assessments. The results were scored by observer and digitally analyzed using ImageJ software.
Our data showed that CsA administration resulted in a significant reduction of AhR expression. This effect was partly blocked in mice coadministrated with B[α]P and CsA. NFATc1 expression was also reduced in CsA-treated animals. Furthermore, CsA inhibited the pathological effects of B[α]P in mouse lung tissue.
AhR expression is dependent on NFATc1 activation, and NFATc1 inhibition remarkably decreases AhR expression. However, it seems that total expression of NFATc1 is not dependent on AhR expression or activation. Moreover, CsA can prevent B[α]P-induced lung tissue damage, and it remarkably decreases NFATc1 expression. The results from this study point toward the molecular interactions of AhR and NFATc1 activation in lung tissue and the benefit of CsA treatment in B[α]P-induced lung damage.
Sulfite, commonly used as a preservative in foods, beverages, and pharmaceuticals, is a very reactive and potentially toxic molecule which is detoxified by sulfite oxidase (SOX). Changes induced by aging may be exacerbated by exogenous chemicals like sulfite. The aim of this study was to investigate the effects of ingested sulfite on visual evoked potentials (VEPs) and brain antioxidant statuses by measuring superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities. Brain lipid oxidation status was also determined via thiobarbituric acid reactive substances (TBARS) in normal- and SOX-deficient aged rats. Rats do not mimic the sulfite responses seen in humans because of their relatively high SOX activity level. Therefore this study used SOX-deficient rats since they are more appropriate models for studying sulfite toxicity. Forty male Wistar rats aged 24 months were randomly assigned to four groups: control (C), sulfite (S), SOX-deficient (D) and SOX-deficient + sulfite (DS). SOX deficiency was established by feeding rats with low molybdenum (Mo) diet and adding 200 ppm tungsten (W) to their drinking water. Sulfite in the form of sodium metabisulfite (25 mg kg–1 day–1) was given by gavage. Treatment continued for 6 weeks. At the end of the experimental period, flash VEPs were recorded. Hepatic SOX activity was measured to confirm SOX deficiency. SOX-deficient rats had an approximately 10-fold decrease in hepatic SOX activity compared with the normal rats. The activity of SOX in deficient rats was thus in the range of humans. There was no significant difference between control and treated groups in either latence or amplitude of VEP components. Brain SOD, CAT, and GPx activities and brain TBARS levels were similar in all experimental groups compared with the control group. Our results indicate that exogenous administration of sulfite does not affect VEP components and the antioxidant/oxidant status of aged rat brains.
Pesticides are omnipresent in environment, water, fruits, and vegetables and are considered as risk factors for human health. Consumers are mainly exposed to pesticides through diet, and the main question to be answered concerns the impact of such exposure on health. In this study, we developed a mouse model to mimic consumer exposure. During gestation and lactation periods, the experimental mouse dams (M) received one of the following treatments: (a) diet-free of pesticides; (b) diet enriched with chlorpyrifos (CPF; 44.0 μg kg–1); c) diet + oral vitamin E (vit. E; α-tocopherol; 200 mg/kg/mouse); and (d) diet enriched with CPF (44.0 μg/kg + oral vit. E (200 mg/kg/mouse). At weaning, pups (P) and dams were killed, and organs as well as blood samples were collected. Compared with control results, CPF induced alteration of measured parameters (e.g. organ weight, alkaline phosphatase, urea, malondialdehyde, superoxide dismutase, and cholinesterase) either in mouse dams or in their offspring. Also, CPF induced histological impairment in kidney, liver, and ovary. Administration of vit. E in conjunction with CPF clearly alleviated deviation of these parameters than those of control ones. In conclusion, a dietary exposure of mice during gestation and lactation to low dose of CPF led to significant changes in the mother but also in the weaned animals that have not been directly exposed to this pesticide. These biological and histological modifications could be reversed by an oral supplementation of vit. E.
Apoptosis triggered by ricin toxin (RT) has previously been associated with certain cellular organellar compartments, but the diversity in the composition of the organellar proteins remains unclear. Here, we applied a shotgun proteomics strategy to examine the differential expression of proteins in the mitochondria, nuclei, and cytoplasm of HeLa cells treated and not treated with RT. Data were combined with a global bioinformatics analysis and experimental confirmations. A total of 3107 proteins were identified. Bioinformatics predictors (Proteome Analyst, WoLF PSORT, TargetP, MitoPred, Nucleo, MultiLoc, and k-nearest neighbor) and a Bayesian model that integrated these predictors were used to predict the locations of 1349 distinct organellar proteins. Our data indicate that the Bayesian model was more efficient than the individual implementation of these predictors. Additionally, a Biomolecular Interaction Network (BIN) analysis was used to identify 149 BIN subnetworks. Our experimental confirmations indicate that certain apoptosis-related proteins (e.g. cytochrome c, enolase, lamin B, Bax, and Drp1) were found to be translocated and had variable expression levels. These results provide new insights for the systematic understanding of RT-induced apoptosis responses.
Our earlier study had shown that low concentrations of monocrotophos (MCP) elicited dopaminergic features of Parkinson’s disease (PD) in the nematode Caenorhabditis elegans. In the present study, the effect of low doses of MCP on the striatal dopaminergic neurons was investigated using the mouse model system. MCP was initially screened for its ability to cause any neurobehavioral deficits and alterations in the dopaminergic system in Swiss albino mice, aged 8 weeks and weighing 25–30 g, with repeated doses at 0.3 and 0.6 mg/kg body weight (b.w.)/day for 7 days and 30 days. Mice were treated with four intraperitoneal injections for every 2 h with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at the dosage of 14 mg/kg b.w. MCP was administered to these mice at the above-mentioned doses for 7 days. Mice administered with MCP alone revealed a significant (p < 0.05) reduction in the dopamine (DA) content at both 7 and 30 days and showed a significant (p < 0.05) increase in neurobehavioral deficits. Interestingly, when MCP was administered for 7 days to MPTP-treated mice, further significant decrease in both DA content and increase in neurobehavioral deficits were apparent. The extent of reactive oxygen species and lipid peroxidation were markedly increased, while the ratio of reduced to oxidized glutathione levels were significantly decreased (p < 0.05) in the treated mice as compared to the control. Significant histopathological alterations and a marked reduction in the number of tyrosine hydroxylase positive cells were evident in striatum of mice treated with higher doses of MCP. These changes were comparable to that seen in mice treated with MPTP and post-administered lower doses of MCP. Our findings suggest that MCP per se has the propensity to induce pathological changes in the dopaminergic neurons as well as augment the degeneration in a compromised nigrostriatal system such as that in PD.
Hepatic fibrosis is an important outcome of chronic liver injury and results in excess synthesis and accumulation of extracellular matrix (ECM) components. Phyllanthin (PLN) isolated from Phyllanthus amarus exhibits strong antioxidative property and protects HepG2 cells from carbon tetrachloride (CCl4)-induced experimental toxicity. The present study reports the antifibrotic potential of PLN. The in vivo inhibitory effect of PLN on CCl4-mediated lipid peroxidation and important profibrotic mediator transforming growth factor β1 and on predominant ECM components collagen and fibronectin were also studied. The results show that PLN acts by suppressing the expression of inflammatory cytokine tumor necrosis factor-α and prevents activation of nuclear factor-B in hepatic tissue. Our study highlights the molecular mechanism responsible for the antifibrotic efficacy of PLN.
Trivalent chromium (Cr) is an environmental contaminant, which is extensively used in tanning industries throughout the world and causes various forms of health hazards in tannery workers. Therefore, a cross-sectional study design was used to evaluate the DNA damage and oxidative stress condition in tannery workers exposed to Cr in North India. The study population comprised 100 male tanners in the exposed group and 100 healthy males (no history of Cr exposure) in the comparable control group. Baseline characteristics including age, smoking, alcohol consumption habits and duration of exposure were recorded via interviewing the subjects. Blood Cr level (measured by atomic absorption spectrophotometry), DNA damage (measured by comet assay) and oxidative stress parameters (malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD)) were estimated in both the groups. As a result of statistical analysis, exposed group showed significantly higher level of Cr (p < 0.0001), DNA damage (p < 0.0001), MDA (p < 0.0001), SOD (p < 0.05) and lower level of GSH (p < 0.001) when compared with controls. Smoking, alcohol consumption habits and age had no significant effect (p > 0.05) on DNA damage and oxidative stress parameters in both the groups. In simple and multiple correlation analysis, DNA damage and oxidative stress parameters showed significant correlation with Cr level and duration of exposure in exposed group. The findings of the present study revealed that chronic occupational exposure to trivalent Cr may cause DNA damage and oxidative stress in tannery workers.
Organophosphate poisoning is a life-threatening condition, which is being responsible for the symptoms due to cholinergic effects. Clinical status and blood levels of cholinesterase are used its diagnosis. While atropine and pralidoxime (PAM) appear as essential medications, hemofiltration treatments and lipid solutions have been widely studied in recent years. In this study, the importance of high-dose atropine therapy and early intervention and novel treatment approaches are discussed. Records of a total of 25 patients treated for organophosphate poisoning in the intensive care unit (ICU) between April 2007 and December 2011 were evaluated retrospectively. Of the 25 patients, 14 (56%) were male and 11 (44%) were female with a mean age of 34.8 ± 17.66 years (range: 14–77 years). The patients were most frequently admitted in June (n = 4) and July (n = 4) (16%). Of the 25 patients, 22 patients (88%) were poisoned by oral intake, two (8%) by inhalation, and one (4%) by dermal route. Of them, 20 patients (80%) took organophosphates intentionally for suicidal purposes, while five (20%) cases poisoned due to accidental exposure. The scores of Glasgow Coma Scale of nine patients (36%) were below 8 point upon admission to hospital. The highest dose of atropine given was 100 mg intravenously on admission and 100 mg/h/day during follow-up. The total dose given was 11.6 g/12 days. A total of 11 patients (44%) were on mechanical ventilation for a mean duration of 5.73 ± 4.83 days. The mean duration of ICU stay was 6.52 ± 4.80 days. Of all, 23 patients (92%) were discharged in good clinical condition and one patient (4%) was referred to another hospital. This study suggests that atropine can be administered until secretions disappear and intensive care should be exerted in follow-up of these patients. In addition, in case of necessity for high doses, sufficient amounts of atropine and PAM should be available in hospitals.
Human exposure to benzene in work environment is a global occupational health problem. It is established that benzene requires to be metabolized to induce its effects. Benzene has been associated with various hematotoxins and carcinogens. The aim of this study was to investigate the effect of benzene on complete blood picture, with emphasis of trans, trans-muconic acid (t,t-MA) as a biomarker of benzene in urine, considering the influence of cigarette smoke. A total of 81 workers (61 males and 20 females) have been occupationally exposed to benzene. In addition, 83 workers (55males and 28 females) were also recruited as a control group. Complete blood picture was analyzed and urinary t,t-MA was determined by liquid chromatography. In addition, creatinine in the urine samples was determined. Levels of blood elements (white blood cells, red blood cells and platelets) were decreased among exposed workers compared with the controls. The urinary level of t,t-MA/creatinine of the exposed workers was elevated especially in the smoking group compared to the controls. This study recommends that complete blood picture and t,t-MA are helpful biomarker tests that should be done to detect the early effects of benzene exposure.
In this investigation, the genotoxic and oxidative effects of water soluble extracts of dung beetles, flying grasshopper and mole crickets have been assessed on cultured human blood cells. The extracts were added to the culture tubes at 12 different concentrations (0–2000 ppm). Micronucleus test was used to monitor the DNA and the chromosomal damage produced by aqueous extracts in vitro. In addition, to assess the oxidative effects, total antioxidant capacity (TAC) and total oxidant status (TOS) levels were also measured. Our results indicated that these extracts did not show genotoxic effects at the tested concentrations. However, the extracts caused dose-dependent alterations in both TAC and TOS levels. Based on the findings, it was concluded that the studied insects can be consumed safely, but it is necessary to consider the cellular damages which are likely to appear depending on oxidative stress at higher concentrations. It has also been suggested that this in vitro approach for oxidative and genotoxicity assessments may be useful to evaluate the potential health risks of edible insects.
Some studies have shown that exposure to electromagnetic field (EMF) may result in structural damage to neurons. In this study, we have elucidated the alteration in the hippocampal function of offspring Wistar rats (n = 8 rats in each group) that were chronically exposed to mobile phones during their gestational period by applying behavioral, histological, and electrophysiological tests. Rats in the EMF group were exposed to 900 MHz pulsed-EMF irradiation for 6 h/day. Whole cell recordings in hippocampal pyramidal cells in the mobile phone groups did show a decrease in neuronal excitability. Mobile phone exposure was mostly associated with a decrease in the number of action potentials fired in spontaneous activity and in response to current injection in both male and female groups. There was an increase in the amplitude of the afterhyperpolarization (AHP) in mobile phone rats compared with the control. The results of the passive avoidance and Morris water maze assessment of learning and memory performance showed that phone exposure significantly altered learning acquisition and memory retention in male and female rats compared with the control rats. Light microscopy study of brain sections of the control and mobile phone-exposed rats showed normal morphology.
Our results suggest that exposure to mobile phones adversely affects the cognitive performance of both female and male offspring rats using behavioral and electrophysiological techniques.
Vanadium (V) is an air pollutant released into the atmosphere by burning fossil fuels. Also, it has been recently evaluated for their carcinogenic potential to establish permissible limits of exposure at workplaces. We previously reported an increase in the number and size of platelets and their precursor cells and megakaryocytes in bone marrow and spleen. The aim of this study was to identify the involvement of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway and thrombopoietin (TPO) receptor, and myeloproliferative leukemia virus oncogene (Mpl), in megakaryocyte proliferation induced by this compound. Mice were exposed twice a week to vanadium pentoxide inhalation (0.02 M) and were killed at 4th, 6th, and 8th week of exposure. Phosphorylated JAK2 (JAK2 ph), STAT3 (STAT3 ph), STAT5, and Mpl were identified in mice spleen megakaryocytes by cytofluorometry and immunohistochemistry. An increase in JAK2 ph and STAT3 ph, but a decrease in Mpl at 8-week exposure was identified in our findings. Taking together, we propose that the morphological findings, JAK/STAT activation, and decreased Mpl receptor induced by V leads to a condition comparable to essential thrombocythemia, so the effect on megakaryocytes caused by different mechanisms is similar. We also suggest that the decrease in Mpl is a negative feedback mechanism after the JAK/STAT activation. Since megakaryocytes are platelet precursors, their alteration affects platelet morphology and function, which might have implications in hemostasis as demonstrated previously, so it is important to continue evaluating the effects of toxics and pollutants on megakaryocytes and platelets.
Background: Aircraft noise is an environmental stressor. A positive relationship exists between noise and high blood pressure. Shift work is an additional hazardous working condition with negative effect on the behavior attitude of workers. Objective: This study aimed at investigating some health hazards for shift work on workers at Cairo International Airport (CIA), Egypt, as a strategic work place, with more than one stressor. Subjects and Methods: Assessment of noise effects were carried out in four working sites at the airport besides control sites. The average noise level in the exposure sites was 106.5 dB compared with 54 dB at the control sites. The study comprised a group of 200 male workers exposed to aircraft noise and 110 male workers not exposed to noise as control group. All workers had full general medical examination after filling specially formulated questionnaire. Hearing impairment, raised blood pressure, headaches, disturbed sleep, and symptoms of anxiety were more prominent among the exposed workers than the control. Symptoms of upper respiratory tract were reported among night shifters of both groups with high tendency for smoking. Thus, night-shift workers at CIA work under more than one stressor. Hypertension and smoking might act as intermediate factors on the causal pathway of complaints, making aircraft noise and night shift acting as two synergistic stressors. Airport workers are in need for aggressive hearing conservation programs. Organization of the working hours schedule is mandatory to avoid excessive noise exposure.
There are many reports on the effects of intravenous lipid emulsion (ILE) as an antidote in drug toxicity. Haloperidol (HAL) is a butyrophenone antipsychotic agent which is highly lipophilic. Hypotension is an important adverse effect of HAL administration and overdose. The aim of this study was to investigate the beneficial hemodynamic effects of ILE on acute HAL poisoning. We used six groups of five male rabbits. Two groups received aseptic distilled water intravenously followed by infusion of 18.6 ml/kg normal saline, as negative control group, or ILE 20% after 0.5 h. The third group received 18.6 ml/kg normal saline after HAL infusion (2.6 mg/kg). The other three groups received ILE 20% solution (6, 12, and 18.6 ml/kg) following HAL (2.6 mg/kg) administration. We measured blood pressure at 0, 0.5, 1, 2, 3, 4, 8, and 24 h after starting HAL administration, from left forelimb using a noninvasive method that was carried out automatically with a neonatal intensive care unit bedside monitor. ILE 20% at the dose of 18 ml/kg could return the reduced mean arterial pressure and diastolic blood pressure sooner than the other doses and normal saline. In conclusion, ILE could reverse HAL-induced hypotension same as the other lipophilic drugs. However, the clinical use of ILE for this purpose needs more evaluation to determine its exact indication and safety.
Flavonoids are important constituents of food and beverages, and several studies have shown that they have neuroactive properties. Many of these compounds are ligands for -aminobutyric acid type A receptors in the central nervous system. This study aimed to investigate the anticonvulsant effects of quercetin (3,3',4',5,7-pentahydroxyflavone), which is a flavonoid found in plants, in rats treated with pentylenetetrazole in acute and chronic seizure models. Single intraperitoneal administration of quercetin did not show anticonvulsive effects against acute seizure. Similarly, multiple oral pretreatment with quercetin did not have protective effects against acute seizure. However, multiple intraperitoneal administration of quercetin (25 and 50 mg/kg) significantly increased time to death compared with the control (p < 0.001). However, quercetin pretreatment had no significant effects on the pattern of convulsion development during all periods of kindling. But on the test day, quercetin (100 mg/kg) could significantly increase generalized tonic–clonic seizure onset (GTCS) and decrease GTCS duration compared with the control (p < 0.01, p < 0.05). We conclude that quercetin has a narrow therapeutic dose range for anticonvulsant activities in vivo, and it has different effects on the seizure threshold. The different effects of quercetin on seizure threshold may occur through several mechanisms.
For improvements in market competitiveness, old brand chemical enterprises did some expansion and reconstruction on the base of original equipment. Because it is the reconstruction on the basis of the existing production equipment, it is bound to raise problems of reutilization existing in pipelines and equipment. A simplified typical chemical factory was established referring the actual workshop layout. Further, trustable accident scenarios were conducted to reveal the diffusion process. In a larger leakage rate, the chlorine leak-affected area in the downwind became larger a bit, also in a relatively shorter time, lethal scope will become larger quickly, resulting in more threats to the lives and properties in the vicinity of the factories. Further, it is not possible that the heavier-than-air effect of the chlorine will inevitably result in a higher concentration for a lower surface than that of higher surface. Actually at a certain height, a relatively higher monitoring surface has a larger diffusion range and a larger concentration than a relatively lower surface. It can be inferred that within a certain height, chlorine diffusion rate closer to the ground would be slower due to existence of turbulence or the relative resistance on the ground.
This study aims to evaluate two proteins derived from the seeds of the plants Cajanus cajan (Leguminosae) and Caesalpinia gilliesii (Leguminosae) for their abilities to ameliorate the toxic effects of chronic doses of acetoaminphen (APAP) through the determination of certain biochemical parameters including liver marker enzymes: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bilirubin. Also, total protein content and hepatic marker enzyme, lactate dehydrogenase were studied. Moreover, liver antioxidants, glutathione (GSH), nitric oxide, and lipid peroxides were determined in this study. Hepatic adenosine triphosphatase (ATPase), adenylate energy charge (ATP, adenosine diphosphate, adenosine monophosphate, and inorganic phosphate), and phosphate potential, serum interleukin-6, tumor necrosis factor-α, and myeloperoxidase were also examined in the present study. On the other hand, histopathological examination of intoxicated and liver treated with both proteins was taken into consideration. The present results show disturbances in all biochemical parameters and hepatic toxicity signs including mild vascular congestion, moderate inflammatory changes with moderate congested sinusoids, moderate nuclear changes (pyknosis), moderate centrilobular necrosis, fatty changes, nuclear pyknosis vascular congestion, and change in fatty centrilobular necrosis liver. Improvement in all biochemical parameters studied was noticed as a result of treatment intoxicated liver with C. gilliesii and C. cajan proteins either paracetamol with or post paracetamol treatment. These results were documented by the amelioration signs in rat's hepatic architecture. Thus, both plant protein extracts can upregulate and counteract the inflammatory process, minimize damage of the liver, delay disease progression, and reduce its complications.
The present study was carried out for the assessment of physiological biosafety and effects of genetically modified (GM) canola on Avena sativa, which is a common weed plant of South Asia. Methanolic extracts of GM and non-GM canola were assessed on seed germination and growth of A. sativa under sterilized conditions. The extracts were treated with 3%, 5%, and 10% concentrations of methanol. Results showed that the extract of GM canola increases the number of roots and root fresh weight. However, root length was significantly decreased. Similarly, a significant rate of increase was observed in shoot fresh weight and shoot length of A. sativa by treatment of GM canola. Emergence percentage, germination index, and emergence rate index show a significant effect of decrease when treated with GM canola.
This study on the effect of genetically modified (GM) and non-GM canola on soybean was carried out for physiological and biochemical biosafety assessment of GM canola. Methanolic extracts of GM and non-GM canola were assessed on seed germination and growth of soybean (Glycine max L.) under sterilized conditions. The extracts applied were of 3, 5, and 10% concentrations. The results showed that methanolic extracts of both GM and non-GM canola improved the germination percentage. However, germination rate index was significantly decreased with concomitant increase in mean germination time of soybean. A significant rate of decrease was observed in root fresh weight while increase in shoot length took place; when treatment of GM canola extracts were applied, however, no effect was observed in shoot fresh weight. A significant increase in protein contents, as well as phenolic, carotenoids, proline, and chlorophyll a content, was observed when different GM canola treatments (3, 5, and 10%) were applied to soybean; however, a significant rate of reduction in chlorophyll b content was observed by the application of GM canola treatment. Similar results were observed for superoxide dismutase, peroxidase, and catalase activities. A significant increase in the sugar content levels was observed when GM canola treatments (3, 5, and 10%) were applied to soybean.
Most of the chemicals in the petrochemical sewages cause oxidative stress in marine organisms. Antioxidant enzymes (catalase (CAT) and superoxide dismutase (SOD)) as biomarkers of oxidative stress and liver histopathological alterations were investigated in the current study to evaluate the toxic effects of petrochemical pollutions in flatfish, Euryglossa orientalis. The enzymatic and histopathological changes were assessed in the liver of E. orientalis from Khowr-e Jafari (one of the creeks from Khowr-e Musa estuary) and Sajafi harbor as polluted and clean areas, respectively. A significant increase in the antioxidant enzyme activities was observed in response to aquatic pollutions of Khowr-e Jafari. Liver lesions were diagnosed and categorized using standard methods. The results of histopathological examinations showed more lesion scores in the fish from Khowr-e Jafari. Various histopathological changes including hepatocyte degeneration, inflammatory lesions, peliosis hepatis and pancreatic acinar cell adenoma, and increase in the number of pigmented macrophage aggregates were observed in the fish from polluted site. It is suggested that activities of CAT and SOD along with semi-quantitative histopathologic analysis of E. orientalis can be used for biomonitoring programs in Persian Gulf.
Natural healing agents are primarily focused to overcome unwanted side effects with synthetic drugs worldwide. In the proposed study, crude extracts and subsequent solvent fractions of Heliotropium strigosum were evaluated for antinociceptive and anticonvulsant activity in animal paradigms. In post acetic acid-induced writhing test, crude extract and fractions (hexane, ethyl acetate, and aqueous) demonstrated marked attenuation of nociception at test doses (50, 100, and 200 mg/kg i.p.). When challenged against thermally induced pain model, pretreatment of extracts exhibited prominent amelioration at test dose (50, 100, and 200 mg/kg i.p.). In both tests, inhibition of noxious stimulation was in a dose-dependent manner, and ethyl acetate fraction was most dominant. However, extracts did not antagonize the seizures and mortality induced by pentylenetetrazole. In conclusion, the extracts of H. strigosum illustrated significant antinociceptive effect in both centrally and peripherally acting pain models.
This study aimed to investigate the protective effects of melatonin against arsenic-induced apoptosis and oxidative stress in rat testes. A total of 27 male rats were divided into 3 groups: control (saline: 5 ml kg-1 day-1, intragastrically), arsenic (sodium arsenite (NaAsO2): 5 mg kg-1 day-1, intragastrically), and arsenic + melatonin (sodium arsenite (NaAsO2): 5 mg kg-1 day-1, intragastrically and melatonin: 25 mg kg-1 day-1, intraperitoneally) group. At the end of 30 days, the rats were killed under anesthesia. Histopathological examination showed that testicular injury mediated by arsenic was ameliorated by the administration of melatonin. The number of apoptotic germ cell was increased, and the number of proliferating cell nuclear antigen (PCNA)-positive germ cell was decreased in testis after arsenic administration. Our data indicate a significant reduction in the activity of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling, and there was a rise in the expression of PCNA in testis of arsenic + melatonin group. The decreased superoxide dismutase, catalase, and glutathione peroxidase activities as well as increased malondialdehyde levels in testis due to arsenic administration were also counteracted by melatonin. These data suggested that melatonin has beneficial effects against arsenic-induced testicular damage by decreasing morphological damage, germ cell apoptosis, lipid peroxidation, and oxidative stress. Our results suggest that melatonin plays a protective role against arsenic-induced testicular apoptosis and oxidative stress.
Polygonatum verticillatum has traditionally been used for various purposes. The present study was aimed to validate the antispasmodic and antidiarrheal properties of crude methanolic extract of rhizomes of P. verticillatum (PR). Isolated rabbit jejunum preparations were suspended in tissue baths to measure the isotonic responses using Power Lab data acquisition system for the antispasmodic activity of PR, while the antidiarrheal activity was conducted in vivo in mice. PR caused complete relaxation of the spontaneous contractions of isolated rabbit jejunum preparations in a dose-dependent mode. A complete inhibition was observed against low potassium (K+; 25 mM)-induced contractions, while the plant extract partially inhibited the high K+ (80 mM)-induced contractions. From a mechanistic point of view, the spasmolytic effect of PR against low K+ was antagonized by glibenclamide similar to the effect of cromakalim, thus showing the presence of constituents in PR mediating spasmolytic activity predominantly through the activation of adenosine triphosphate-sensitive K+ channels. When tested against castor oil-induced diarrhea in mice, oral administration of the plant extract manifested marked antidiarrheal activity at the doses of 500 and 1000 mg/kg similar to loperamide. This study provided a pharmacological basis for the medicinal use of PR in abdominal colic and diarrhea.
The purpose of the current study was to estimate the antioxidant profile of two compounds, diosgenin and santonin, isolated from Polygonatum verticillatum rhizomes. Stable free radical, 2, 2-diphenyl-1-picrylhydrazyl and reducing power assays were employed for this purpose. The results showed profound free radical scavenging effect of both diosgenin and santonin in a concentration-dependent manner. The calculated half maximal inhibitory concentration (IC50) values for both diosgenin and santonin was 65.80 and 50.03 μg/ml, respectively. Similarly, in reducing power assay, diosgenin and santonin exhibited marked quenching effect. The corresponding IC50 values for both the compounds were 62.10 and 46.40 μg/ml, respectively. In conclusion, both the isolated compounds have strong antioxidant potential, which is consistent with the results of the extracts of the plant.
The current project was designed to evaluate the anti-inflammatory activity of crude extract of Heliotropium strigosum and its subsequent solvent fractions in post carrageenan-induced edema and post xylene-induced ear edema at 50, 100, and 200 mg/kg intraperitoneally. The results revealed marked attenuation of edema induced by carrageenan injection in a dose-dependent manner. The ethyl acetate fraction was most dominant with 73.33% inhibition followed by hexane fraction (70.66%). When the extracts were challenged against xylene-induced ear edema, again ethyl acetate and hexane fractions were most impressive with 38.21 and 35.77% inhibition, respectively. It is concluded that various extracts of H. strigosum possessed strong anti-inflammatory activity in animal models.
The current study was aimed to scrutinize acetylcholinesterase (AchE) inhibitory profile of two antidepressants, diazepam and phenobarbitone. The experimental designed was based on Michaelis–Menten parameters (apparent Michaelis constant (aKm) and apparent maximum velocity (aVm)) that estimate inhibition (%) as well as the type of inhibition (mechanism). The results showed marked inhibition of AchE by diazepam and the values of aKm and aVm were 65.5% and 52.63%, respectively. These values suggested a competitive type of antagonism for diazepam. Similar trend of antagonism was shown by phenobarbitone when it was subjected to the challenge of AchE with aKm and aVm values of 51.99% and 71.80%, respectively. It is concluded that diazepam and phenobarbitone exhibited prominent AchE attenuation apart from their well-established antidepressant activity, which could be more useful in related diseased conditions.
Over expression of lipoxygenase (LOX) and urease has already contributed to the pathology of different human disease. Targeting the inhibition of these enzymes has proved great clinical utility. The aim of the present study was to scrutinised the inhibitory profile of the aerial parts of the Polygonatum verticillatum enzyme against LOX, urease, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using standard experimental protocols. When checked against lipoxygenase, the extracts revealed significant attenuation. Of the tested extracts, the ethyl acetate fraction was the most potent (half-maximal inhibitory concentration (IC50): 97 µg/mL) followed by aqueous fraction IC50: 109 µg/mL). Regarding urease inhibition, n-butanol was the most potent fraction (IC50: 97 µg/mL). However, the extracts did not show significant inhibition on AChE and BChE. In the preliminary phytochemical tests, the aerial parts of the plant showed the presence of saponins, alkaloids, flavonoids, phenols, tannins and terpenoids. The current findings could be attributed to these groups of compounds.
The current study was aimed to assess antibacterial, antioxidant and cytotoxic activity of total saponin, alkaloid and sterol contents of Joshanda decoction followed by its constituent’s analysis via thin layer chromatography (TLC). Saponins and alkaloids showed prominent antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Bacillus cereus and Klebsiella pneumoniae whereas sterols only against S. aureus. Saponin and alkaloid contents of 97 and 108 µg/ml, respectively, showed prominent free radical scavenging activity against 1,1-diphenyl-2-picrylhidrazyl, with mild cytotoxicity in brine shrimp cytotoxic test. Under ultraviolet light at 254 nm, TLC of total saponins showed eight different compounds, total sterols comprising three while total alkaloids two compounds of various polarities. It is concluded that the various contents of Joshanda decoction possess outstanding susceptibility against bacteria implicating primarily upper respiratory tract infections augmented by strong antioxidant activity.
This study describes the cytotoxic and phytotoxic activities of the crude extract of Heliotropium strigosum and its resultant fractions. In brine shrimp toxicology assays, profound cytotoxicity was displayed by ethyl acetate (LD50 8.3 μg/ml) and chloroform (LD50 8.8 μg/ml) fractions, followed by relatively weak crude methanolic extract of H. strigosum (LD50 909 μg/ml) and n-hexane fraction (LD50 1000 μg/ml). In case of phytotoxicity activity against Lemna acquinoctialis, highest phytotoxic effect was showed by ethyl acetate fraction (LD50 91.0 μg/ml), while chloroform fraction, plant crude extract and n-hexane, respectively, caused 50%, 30.76 ± 1.1% and 30.7 ± 1.1% inhibitory action at maximum concentration used, that is, 1000 μg/ml. These data indicates that H. strigosum exhibits cytotoxic and phytotoxic potential, which explore its use as anticancer and herbicidal medicine. The ethyl acetate and chloroform fractions were more potent for the evaluated toxicity effects, thus recommended for isolation and identification of the active compounds.
We investigated the relationship between dibutyl phthalate (DBP)-induced hypomethylation of the c-Myc promoter region (as evident in our early study) and the expression of c-Myc and DNMT1 genes (at messenger RNA (mRNA) and protein level) in the rat liver. Male Wistar rats received DBP in 1, 3, or 14 daily doses of 1800 mg kg-1 body weight. Levels of DNMT1, c-Myc mRNA, and proteins were detected using real-time polymerase chain reaction and Western blot analysis, respectively. Our findings indicate that DBP caused an increase in mRNA levels of c-Myc at all time points. The results showed that protein levels of c-Myc in rat liver also increased significantly by DBP treatment, which were more pronounced at last time point (after 14 doses). Furthermore, overexpression of DNMT1gene have been found after one dose of DBP, which was confirmed at the protein level by Western blot analysis. Reduced levels of DNMT1mRNA and proteins (3 and 14 doses) were coordinated with depletion DNA synthesis (reported previously). Based on our previous results and those presented here, the following conclusion could be drawn: (1) DBP exerted biological activity through epigenetic modulation of c-Myc gene expression; (2) it seems possible that DBP-induced active demethylation of c-Myc gene through mechanism(s) linked to generation of reactive oxygen species by activated c-Myc; and (3) control of DNA replication was not directly dependent on c-Myc transcriptional activity and we attribute this finding to DNMT1gene expression which was tightly coordinated with DNA synthesis.
The current study was designed to assess the phytochemical profile, antibacterial, and antifungal activities of the crude methanol extract of the aerial parts of Polygonatum verticillatum (PA) and its various subsequent solvent fractions using agar well diffusion, agar tube dilution, and microdilution methods. Phytochemical analysis showed positive for different chemical groups and also contained marked quantity of saponin and flavonoid contents. Significant antibacterial activity was observed against various tested pathogenic bacteria. The only susceptible Gram-positive bacterium was Bacillus subtilis and their minimum inhibitory concentrations (MICs) measured ranged from 11–50 µg/ml. The sensitive Gram-negative bacteria were Salmonella typhi and Shigella flexeneri. The estimated MICs were in the range of 2–7 µg/ml and 8–50 µg/ml for S. typhi and S. flexeneri, respectively. However, the antifungal activity of the plant was limited to Microsporum canis and their MICs ranged from 60 to 250 µg/ml. Our study confirmed significant antibacterial potential of the plant and substantiated its folk use in dysentery and pyrexia of multiple origins.
Diabetic peripheral neuropathy (DPN) is widely considered as a degenerative complication of diabetic patients. The clinical effectiveness of folic acid (FA) on DPN is uncertain. The objective of the present study was to determine the effect of FA in DPN using electromyography (EMG), histopathological examination, immunohistochemistry, inclined plane test, and malondialdehyde (MDA) levels as a marker for lipid peroxidation in experimental diabetic rats. A total of 21 Sprague Dawley rats were randomly divided into 3 groups: control group, diabetes group, and FA-treated group. In EMG, compound muscle action potential (CMAP) amplitude in the sciatic nerve was lower in the diabetes group compared with the control group. CMAP amplitude in the sciatic nerve was higher in the FA-treated group when compared with the diabetes group. Distal latency and CMAP duration in the sciatic nerve were lower in the FA-treated group when compared with the diabetes group. In histopathological examination of the sciatic nerve, peripheral fibrosis was present in the diabetic group; the fibrosis was lower in the FA-treated group. In comparison with the diabetes group, the expression of nerve growth factor (NGF) was higher in the FA-treated group. The scores for the inclined plane test were lower in the diabetes group and higher in the FA-treated group than the control group. The MDA levels were significantly lower in the FA-treated group when compared with the diabetes group.
The study suggests that FA can protect diabetic rats against DPN and that the underlying mechanism for this may be related to improvement of the expression of NGF and lower MDA levels.
Copper oxide nanoparticles (CuO NPs) are of great interest in nanoscience and nanotechnology because of their broad industrial and commercial applications. Therefore, toxicity of CuO NPs needs to be thoroughly understood. The aim of this study was to investigate the cytotoxicity, genotoxicity, and oxidative stress induced by CuO NPs in human lung epithelial (A549) cells. CuO NPs were synthesized by solvothermal method and the size of NPs measured under transmission electron microscopy (TEM) was found to be around 23 nm. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) and lactate dehydrogenase (LDH) assays showed that CuO NPs (5–15 µg/ml) exert cytotoxicity in A549 cells in a dose-dependent manner. Comet assay suggested concentration-dependent induction of DNA damage due to the exposure to CuO NPs. The comet tail moment was 27% at 15 µg/ml of CuO NPs, whereas it was 5% in control (p < 0.05). The flow cytometry data revealed that CuO NPs induced micronuclei (MN) in A549 cells dose dependently. The frequency of MN was 25/103 cells at 15 µg/ml of CuO NPs, whereas it was 2/103 cells for control. CuO NPs were also found to induce oxidative stress in a concentration-dependent manner, which was indicated by induction of reactive oxygen species (ROS) and lipid peroxidation along with glutathione depletion. Moreover, MN induction and DNA damage were significantly correlated with ROS (R2 = 0.937 for ROS vs. olive tail moment, and R2 = 0.944 for ROS vs. MN). Taken together, this study suggested that CuO NPs induce genotoxicity in A549 cells, which is likely to be mediated through ROS generation and oxidative stress.
Chemotherapy-induced acral erythema (CIAE) is a cutaneous response to diverse chemotherapeutic drug administration. These drugs cause symmetrical and painful erythema of palmoplantar surfaces. Bulla formation, desquamation, and subsequent reepithelialization may occur. Commonly, the lesions slowly resolve over 7–15 days, through desquamation, followed by regeneration of the skin. Here, we described a case of CIAE, with involvement of face and neck in a patient treated for breast cancer using a number of chemotherapeutic agents. Face involvement in CIAE has not been previously reported in the literature.
The impact of elevated blood lead level on some haematological parameters was studied in the field force of Lahore traffic police, in Pakistan. The blood samples were tested for total leucocytes count (TLC) and differential leucocytes count in the persons with high and low blood lead levels. The TLC and percentage of neutrophils and eosinophils were observed as being significantly elevated in the policemen. No significant change was observed in the percentage of lymphocytes, while the percentage of monocytes was observed as being significantly less in the field force of traffic police.
Thyroid hormones play a complex role in the toxicity of hexachlorobenzene (HCB) and related compounds. Time–course and dose–response experiments for free- and total thyroxine (T4) and triiodothyronine (T3) plasma levels for thyroid-stimulating hormone (TSH) and thyroid gland histomorphology were determined in male Wistar rats. Also, we examined the possible reversibility of changes noted after removal of HCB. Rats treated with this organochlorine compound resulted in a hypertrophy of the thyroid gland and altered thyroid function by decreasing significantly the levels of total- and free T4 in a dose-dependent manner (total T4: 28 and 51%; free T4: 21 and 37%), and this decrease was seen as early as 21 days and thereafter. Free T3 was also decreased by 21% with the highest dose starting from day 21. No significant changes were observed in the circulating levels of total T3. In response to the decrease of thyroid hormones, a dose-dependent increase of TSH levels (27 and 31%, respectively, for 4 mg and 16 mg/kg of HCB body weight) was observed after 21 days of HCB treatment. We have observed a hypertrophy and hyperplasia of follicular cells and a decrease in colloid volume in histological picture. When HCB was removed and changed by vehicle, the thyroid relative weight and plasma TSH continued to rise and serum thyroid hormones remained suppressed. These findings suggest that subchronic exposure of rats to HCB induced an irreversible hypothyroidism state.
This study aimed to observe the possible protective effects of resveratrol (RSV) against the damage of di-n-butyl phthalate (DBP) on the testis. The study was conducted in 6 groups of rats with 6 animals in each group aged 20 days. The groups include group 1: control group; group 2: solvent (carboxymethylcellulose (CMC), 10 ml/kg); group 3: 500 mg/kg/day DBP; group 4: 500 mg/kg/day DBP + 20 mg/kg/day RSV; group 5: 1000 mg/kg/day DBP; and group 6: 1000 mg/kg/day DBP + 20 mg/kg/day RSV. Groups were treated by gavage for 30 days. Indirect immunohistochemical staining was performed with c-kit, AT1, and ER-α antibodies. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate–biotin nick-end labeling (TUNEL) method was used for apoptosis. It was found in the DBP-applied groups the C-kit immunostaining, which is parallel to increasing dose, decreased in comparison with the control. C-kit reactivity was similar to that of the control group in the group applied with 500 mg/kg/day + RSV; however, the reactivity was not same in the 1000 mg/kg/day DBP-applied group. It was observed that the reactivity of AT1 increased in the DBP-applied groups. RSV reversed these changes with its protective effects. While there was not much difference between the groups in terms of estrogen receptor reactivity, it was observed that the high dose of DBP reduced the level of estrogen receptor and the resveratrol was not at enough levels in all doses. In TUNEL analysis, high doses of DBP increased the apoptosis in all types of cells; nevertheless, the resveratrol application decreased the apoptosis in the low-level DBP dose. In the statistical analysis, while the length of epithelium and the diameter of seminiferous tubules decreased for all the other groups, it reverted to its original state in the RSV-applied groups. In conclusion, DBP (with increasing dose) administration caused cycle and hormonal changes in testis, resveratrol were recovered the cyclic changes but in hormonal changes, RSV is efficient too but inadequate.
The present work aims to evaluate the protective and ameliorative effects of two plant-derived proteins obtained from the seeds of Cajanus cajan and Caesalpinia gilliesii (Leguminosae) against the toxic effects of acetaminophen in kidney after chronic dose through determination of certain biochemical markers including total urea, creatinine, and kidney marker enzyme, that is, glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In addition histopathological examination of intoxicated and treated kidney with both proteins was performed. The present results show a significant increase in serum total urea and creatinine, while significant decrease in GAPDH. Improvement in all biochemical parameters studied was demonstrated, which was documented by the amelioration signs in rats kidney architecture. Thus, both plant protein extracts can counteract the nephrotoxic process, minimize damage to the kidney, delay disease progression, and reduce its complications.
Background: Acute pesticide poisoning is a major public health problem in the world. Most pesticides are toxic to human beings, because of diverse components resulting in different reaction.Objective: As clinicians identify various symptoms due to pesticide poisoning, it is necessary for the diagnosis and treatment for treating such toxins. Accidents associated with acute avermectins poisoning are rarely reported, especially self-induced nystagmus. In the present study, a case of human abamectin poisoning with relevant toxic effects has been reported.Conclusions: Acute avermectins poisoning-induced nystagmus may be affected due to the vestibular cerebellar system, but the exact mechanism and pharmacological basis is still worthy of further study.
Excessive production of free radicals can result in tissue damage, which mainly involves generation of hydroxyl radical and other oxidants. Such free radical-induced cell damage appears to play a major role in the pathogenesis of many diseases. Probiotics have been used therapeutically to modulate immunity, improve digestive processes, lower cholesterol, treat rheumatoid arthritis, and prevent cancer. The proposed research was designed to evaluate the changes in oxidative and antioxidative profile in addition to metabolic-related hormones of living animal model, which may generally affect the health status. Two groups of rabbits (10 animals each) were allocated in hygienic cages of controlled animal house. Control group received standard diet, and the other group received the same diet containing one probiotic for 30 days. Lactate dehydrogenase (LDH) activity in leukocytes, blood glucose, reduced glutathione (GSH), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were estimated in different tissues. Malondialdehyde (MDA) and total proteins were also determined in different tissues. Certain hormones related to metabolism and growth were also evaluated. Leukocytic LDH activity was significantly increased along with nonsignificant increase of blood glucose in probiotics-fed animals. Results showed significant decreases in the levels of triiodothyronine and thyroid-stimulating hormone but showed significant elevations in thyroxine, insulin, growth hormone, and testosterone levels in animals fed with probiotics. Total proteins content was highly significantly elevated in liver, kidneys, and muscles of probiotic-administered animals. Microsomal GSH level was significantly decreased only in skeletal muscles of probiotic-treated animals. MDA was significantly lowered in animal tissues fed with probiotics. GSH-Px activity was elevated in hepatic and muscular microsomes of probiotic-supplemented animals while it was nonsignificantly increased in renal microsomes. Microsomal SOD activity was elevated in liver, kidneys, and skeletal muscles of probiotics-administrated animals. It is concluded that supplementation of probiotic may enhance antioxidant efficacy and scavenge free radicals and thus may be used as a preventive measure for protection against free radicals-induced disorders.
Screening of the toxic effect of a high oral melamine dose (30,000 ppm supplemented in the diet) was performed for 28 days on male rats. The morphology, anatomy, complete blood count (CBC), serum electrolytes, kidney function, serum proteins, serum bilirubin, serum liver enzymes, catalase, glutathion-S-transferase, lipid peroxide, serum melamine concentration, total body weight, food intake, food efficiency ratio (FER), body weight gain percentage (BWG%), body weight gain, water consumption, and histopathological examinations of kidney, urinary bladder, testis, liver, heart, and spleen were investigated. The melamine-supplemented rats turned yellow and showed different degrees of hypertrophy and congestion, particularly the kidney and the ureter as a result of melamine toxicity. The CBC showed minimal changes in the melamine-supplemented groups. Na and Cl were decreased, whereas K, P, and Ca were increased. Serum creatinine, uric acid, and urea were elevated. Liver function enzymes were nonsignificantly affected. Catalase and glutathion-S-transferase were decreased, whereas lipid peroxide was increased in the kidney tissue homogenate. It was also noted that serum protein was decreased and serum bilirubin was increased. Histopathologically, most examined organs were severely injured specially the kidneys, liver, and testes.
The goal of this study was to examine the neuroprotective effect of ebselen against intracerebroventricular streptozotocin (ICV-STZ)-induced oxidative stress and neuronal apoptosis in rat brain. A total of 30 adult male Sprague-Dawley rats were randomly divided into 3 groups of 10 animals each: control, ICV-STZ, and ICV-STZ treated with ebselen. The ICV-STZ group rats were injected bilaterally with ICV-STZ (3 mg/kg) on days 1 and 3, and ebselen (10 mg/kg/day) was administered for 14 days starting from 1st day of ICV-STZ injection to day 14. Rats were killed at the end of the study and brain tissues were removed for biochemical and histopathological investigation. Our results demonstrated, for the first time, the neuroprotective effect of ebselen on Alzheimer’s disease (AD) model in rats. Our present study, in ICV-STZ group, showed significant increase in tissue malondialdehyde levels and significant decrease in enzymatic antioxidants superoxide dismutase and glutathione peroxidase in the frontal cortex tissue. The histopathological studies in the brain of rats also supported that ebselen markedly reduced the ICV-STZ-induced histopathological changes and well preserved the normal histological architecture of the frontal cortex tissue. The number of apoptotic neurons was increased in frontal cortex tissue after ICV-STZ administration. Treatment of ebselen markedly reduced the number of degenerating apoptotic neurons. The study demonstrates the effectiveness of ebselen, as a powerful antioxidant, in preventing the oxidative damage and morphological changes caused by ICV-STZ in rats. Thus, ebselen may have a therapeutic value for the treatment of AD.
Diazinon (DZN), a commonly used agricultural organophosphate insecticide, is one of the major concerns for human health. This study was planned to investigate neurotoxic effects of subacute exposure to DZN in adult male Wistar rats. Animals received corn oil as control and 15 and 30 mg/kg DZN orally by gastric gavage for 4 weeks. The cerebrum malondialdehyde and glutathione (GSH) contents were assessed as biomarkers of lipid peroxidation and nonenzyme antioxidants, respectively. Moreover, activated forms of caspase 3, -9, and Bax/Bcl-2 ratios were evaluated as key apoptotic proteins. Results of this study suggested that chronic administration of DZN did not change lipid peroxidation and GSH levels significantly in comparison with control. Also, the active forms of caspase 3 and caspase 9 were not significantly altered in DZN-treated rat groups. Moreover, no significant changes were observed in Bax and Bcl-2 ratios. This study indicated that generation of reactive oxygen species was probably modulated by intracellular antioxidant system. In conclusion, subacute oral administration of DZN did not alter lipid peroxidation. Moreover, apoptosis induction was not observed in rat brain.
Atrazine (AZ) and glyphosate (GL) are herbicides that are widely applied to cereal crops in Egypt. The present study was designed to investigate the response of the snail Biomphalaria alexandrina (Mollusca: Gastropoda) as a bioindicator for endocrine disrupters in terms of steroid levels (testosterone (T) and 17β-estradiol (E)), alteration of microsomal CYP4501B1-like immunoreactivity, total protein (TP) level, and gonadal structure after exposure to sublethal concentrations of AZ or GL for 3 weeks. In order to study the ability of the snails’ recuperation, the exposed snails were subjected to a recovery period for 2 weeks. The results showed that the level of T, E, and TP contents were significantly decreased (p ≤ 0.05) in both AZ- and GL-exposed groups compared with control (unexposed) group. The level of microsomal CYP4501B1-like immunoreactivity increased significantly (p ≤ 0.05) in GL- and AZ-exposed snails and reach nearly a 50% increase in AZ-exposed group. Histological investigation of the ovotestis showed that AZ and GL caused degenerative changes including azoospermia and oocytes deformation. Interestingly, all the recovered groups did not return back to their normal state. It can be concluded that both herbicides are endocrine disrupters and cause cellular toxicity indicated by the decrease of protein content and the increase in CYP4501B1-like immunoreactivity. This toxicity is irreversible and the snail is not able to recover its normal state. The fluctuation of CYP4501B1 suggests that this vertebrate-like enzyme may be functional also in the snail and may be used as a biomarker for insecticide toxicity.
A bacterium was isolated from the river of Oued Hamdoun (Tunisia), and its phenotypic features, physiological and chemotaxonomic characteristics and phylogenetic analysis of 16S ribosomal RNA sequence revealed it as Pseudomonas peli (P. peli). Chlorpyrifos ethyl (CP) was used as the sole source of carbon and energy by P. peli, and it was cometabolised in the presence of glucose. CP was completely degraded by P. peli after 96 h of shake incubation. High-performance liquid chromatography analysis indicated that the biodegradation kinetics was not affected by the addition of glucose into the culture medium. In the present study, only transient accumulation of one major no-identified product was observed after 48 h of incubation, with no other persistent metabolites detected. Cytotoxicity of CP, before and after biodegradation with P. peli, was evaluated in vitro using the MTT-colorimetric assay against three human cancer cell lines (A549, lung cell carcinoma, HT29, colon adenocarcinoma and MCF7, breast adenocarcinoma). CP reduced viability of all human cell lines in a dose-dependent manner. Its activity was very remarkable against A549 cell line. However, cytotoxicity strongly decreased in CP obtained after incubation with P. peli. Hence, we conclude that when incubated under appropriate conditions, P. peli has a metabolism that completely detoxifies CP.
This article investigates the ability of Pseudomonas peli to treat industrial pharmaceuticals wastewater (PW). Liquid chromatography–mass spectrometry (MS)/MS analysis revealed the presence, in this PW, of a variety of antibiotics such as sulfathiazole, sulfamoxole, norfloxacine, cloxacilline, doxycycline, and cefquinome. P. peli was very effective to be grown in PW and inducts a remarkable increase in chemical oxygen demand and biochemical oxygen demand (140.31 and 148.51%, respectively). On the other hand, genotoxicity of the studied effluent, before and after 24 h of shaking incubation with P. peli, was evaluated in vivo in the Mediterranean wild mussels Mytilus galloprovincialis using comet assay for quantification of DNA fragmentation. Results show that PW exhibited a statistically significant (p < 0.001) genotoxic effect in a dose-dependent manner; indeed, the percentage of genotoxicity was 122.6 and 49.5% after exposure to 0.66 ml/kg body weight (b.w.); 0.33 ml/kg b.w. of PW, respectively. However, genotoxicity decreased strongly when tested with the PW obtained after incubation with P. peli. We can conclude that using comet assay genotoxicity end points are useful tools to biomonitor the physicochemical and biological quality of water. Also, it could be concluded that P. peli can treat and detoxify the studied PW.
The use of pesticides is widespread in agricultural activities. These pesticides may contaminate the irrigation and drainage systems during agriculture activities and pests’ control and then negatively affect the biotic and a biotic component of the polluted water courses. The present study aimed to evaluate the effect of the pesticides diazinon and profenfos on some biological activities of Biomphalaria alexandrina snails such as fatty acid profile, some antioxidant enzymes (thioredoxin reductase (TrxR), sorbitol dehydrogenase (SDH), superoxide dismutase (SOD), catalase (CAT) as well as glutathione reductase (GR) and lipid peroxidation (LP)) and protein patterns in snails' tissues exposed for 4 weeks to LC10 of diazinon and profenfos. The results showed that the two pesticides caused considerable reduction in survival rates and egg production of treated snails. Identification of fatty acid composition in snail tissues treated with diazinon and profenfos pesticides was carried out using gas–liquid chromatography (GLC). The results declared alteration in fatty acid profile, fluctuation in percentage of long chain and short chain fatty acid contributions either saturated or unsaturated ones, and a decrease in total lipid content in tissues of snails treated with these pesticides. The data demonstrate that there was a significant inhibition in the activities of tissues SOD, CAT, glutathione reductase (GR), TrxR, and SDH in tissues of treated snails, while a significant elevation was detected in LP as compared to the normal control. On the other hand, the electrophoretic pattern of total protein showed differences in number and molecular weights of protein bands due to the treatment of snails. It was concluded that the residues of diazinon and profenfos pesticides in aquatic environments have toxic effects on B. alexandrina snails.
Carvacrol (CVC), a major constituent of genera Origanum and Thymus, is such a substance that has attracted attention because of its wide variety of beneficial biological activities such as antibacterial, antifungal, and anticancer effects. However, there are limited data on the cytogenetic and antioxidant effects of CVC in cultured human blood cells. The aim of this study was to investigate for the first time the genetic, oxidative, and cytotoxic effects of CVC in cultured human blood cells (n = 5). Human blood cells were treated with CVC (0–200 mg/L) for 24 and 48 h and then cytotoxicity detected by lactate dehydrogenase (LDH) release and (3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide) (MTT) assay, while DNA damage was also analyzed by micronucleus (MN) assay, chromosomal aberration (CA) assay and 8-oxo-2-deoxyguanosine (8-OH-dG) level. In addition, biochemical parameters (total antioxidant capacity [TAC] and total oxidative stress [TOS]) were examined to determine the oxidative effects. The results of LDH and MTT assays showed that CVC (at concentrations above 100 mg/L) decreased cell viability. In our in vitro test systems, it was observed that CVC had no mutagenic effects on human lymphocytes. On the other hand, CVC (at 50, 75, and 100 mg/L) treatment caused statistically important (p < 0.05) increases in TAC and TOS levels (at 150 and 200 mg/L) on human lymphocytes. In conclusion, CVC can be a new resource of therapeutics as recognized in this study with their nonmutagenic and antioxidant features.
This study aimed to investigate the potential beneficial effects of the montelukast (ML) on oxidative stress and histological alterations in liver tissues and cytokine levels in rats intoxicated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Rats were divided randomly into four equal groups (control, TCDD, ML, TCDD + ML). TCDD were administered by gavages dissolved in corn oil at the doses of 2 µg/kg/week, and ML was given intraperitoneally at the dose of 10 mg/kg/day. Oxidative status, histological alterations, and cytokine levels were analyzed on day 60. The results showed that although TCDD induced oxidative stress via significant increase in formation of thiobarbituric acid reactive substance, it caused a significant decline in glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) levels in liver. Besides, TCDD led to significant histopathological damage in liver and serum cytokine levels alterations (increase in tumor necrosis factor α and interleukin 1β levels). In contrast, ML treatment reversed oxidative effects of TCDD by increasing the levels of GSH, CAT, and SOD and decreasing the formation of TBARS. Also, it can normalize the levels of histological and cytokine alterations induced by TCDD. In conclusion, it was determined that TCDD exposure caused adverse effects on cytokine levels, histological alterations, and oxidative stress in rats. However, ML treatment partially eliminated toxic effects of TCDD. Thus, it was judged that coadministration of ML with TCDD may be useful to attenuate the negative effects of TCDD.
This research work documents the comparative impact of genetically modified (GM) (insect resistance) and non modified maize (Zea mays L.) on growth and germination of succeeding crop wheat (Triticum aestivum L.) and associated weed (Avena fatua L.). The aqueous extracts of both the GM and non-GM maize exhibited higher phenolic content than that of methanolic extracts. Germination percentage and germination index of wheat was significantly decreased by GM methanolic extract (10%) as well as that of non-GM maize at 3% aqueous extract. Similarly germination percentage of weed (Avena fatua L.) was significantly reduced by application of 3% and 5% methanolic GM extracts. All extracts of GM maize showed non-significant effect on the number of roots, root length and shoot length per plant but 5% and 10% methanolic extracts of non-GM maize significantly increased the number of roots per plant of wheat seedling. Similarly, 10% methanolic extract of GM maize significantly increased the number of roots per plant of weed seedling. Methanolic extracts of GM and non-GM maize (3% and 5%) significantly decreased the protease activity in wheat as compared to untreated control.
Background/aim: Doxorubicin (DOX) is a widely used and potent chemothe- rapeutic agent. However, serious dose-limiting toxicity through generation of free oxygen radicals is a commonly encountered clinical problem. The aim of the current study was to assess the protective role of onion (Allium cepa) extract (ACE) against DOX-induced hepatotoxicity in rats. Method: A total of 24 rats were randomly divided into 3 equal experi- mental groups: (1) DOX; (2) ACE + DOX; and (3) control groups. ACE was gi- ven orally as 1 mL of fresh ACE juice for 14 consecutive days followed by DOX injection. DOX was injected intraperitoneally in a single dose of 30 mg/kg body weight to induce hepatotoxicity, and the rats were killed after 48 h from injec- tion. Control group was given saline only. Results: In the ACE pretreated group (ACE + DOX), serum aspartate transaminase, alanine transaminase, and tissue malondialdehyde and gluta- thione levels were significantly lower, while superoxide dismutase and gluta- thione peroxidase were higher compared with the DOX group. The histopatho- logical examination of liver specimens revealed parenchymal necrosis, proli- feration of biliary duct in DOX group; while ACE pretreatment provided marked reduction in these changes. Conclusion: Our study indicates that pretreatment with ACE protects against DOX-induced hepatotoxicity due to the antioxidant properties of ACE. Further studies on efficacy of antioxidant treatment by ACE in DOX-mediated toxicity and underlying mechanisms would provide a better explanation.
The work aimed to evaluate the nanoalumina toxicity on the histological architecture, some haematological and biochemical aspects in male albino rats, during acute and sublethal experiments. Rats, in acute experiments, were injected with a single-acute dose of 3.9 g or 6.4 g or 8.5 g of aluminium oxide (Al2O3) kg-1, whereas those of sublethal were injected with 1.3 g of Al2O3 kg-1 2 days-1. One-way analysis of variance indicated that injected doses and the experimental periods were significantly affected by haemoglobin (Hb) content; haematocrit value (Hct); white blood cell (WBC) count; blood platelet (Plt) count; mean corpuscular volume (MCV); mean corpuscular Hb (MCH) and MCH concentration (MCHC). In acute experiments, Hct, WBC count, MCV and Plt were significantly higher than the corresponding controls, whereas Hb, MCH and MCHC markedly decreased. In comparison with the related controls after 1, 3 and 7 days post-injection, red blood cell count, Hb, Hct, WBC count, Plt and MCV were significantly increased, but begun to decrease after 14 or/and 28 days and were associated with a marked decrease in MCH and MCHC. In serum of rats injected with acute or sublethal dose, the concentrations of total protein (TP) and total lipid (TL) were significantly lesser than the corresponding controls, whereas the levels of urea, uric acid, creatinine and the activities of aspartate aminotransferase and alanine aminotransferase were markedly increased. The injected doses were directly proportional with all the studied biochemical parameter, except the TL and TP that exhibited a negative correlation. Histologically, the highest acute and sublethal doses of nanoalumina caused hepatic irregular disarray, necrosis to the hepatic and Kupffer cells that are associated with congested blood sinusoids. The renal tissues characterized by the appearance of inter-tubular congestion that is accompanied by the dilation of the vascular glomeruli that completely occupied Bowman’s capsule and accompanied with partial disappearance of the renal tubule’s brush border. The brain showed a progressive degeneration of neurons in both the experiments.
This study aimed to investigate the antioxidant properties of different fractions obtained from the fruits of Lawsonia inermis, a widely used medicinal plant, against carbon tetrachloride (CCl4)-induced oxidative stress in rat liver. The results show that several fractions obtained from L. inermis fruits possessed important antioxidant activity. Among them, the ethyl acetate (EA) fraction showed the highest antioxidant activity. Then, EA fraction was selected for the purification of potential antioxidant compounds. The hepatoprotective effects of EA fraction and its most active constituent, gallic acid (GA), were evaluated against CCl4-induced hepatotoxicity in rats. CCl4 induced oxidative stress by a significant rise in serum marker enzymes. However, pretreatment of rats with EA fraction of fruits of L. inermis at a dose of 250 mg kg-1 body weight and GA significantly lowered some serum biochemical parameters (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase) in treated rats. A significant reduction in hepatic thiobarbituric acid reactive substances and an increase in antioxidant enzymes namely superoxide dismutase, catalase, and glutathione peroxidase by treatment with plant extract and GA, against CCl4-treated rats, were observed. Histopathological examinations showed extensive liver injuries, characterized by extensive hepatocellular necrosis, vacuolization, and inflammatory cell infiltration. This potential antioxidant activity is comparable to those of the major purified antioxidant compound, GA. Based on these results, it was observed that fruits of L. inermis protect liver from oxidative stress induced by CCl4 and thus help in evaluation of traditional claim on this plant.
Pesticides have been shown in several studies to be the leading candidates of environmental toxins and may contribute to the pathogenesis of several neurodegenerative diseases. Ziram (zinc-bis(dimethyldithiocarbamate)) is an agricultural dithiocarbamate fungicide that is used to treat a variety of plant diseases. In spite of their generally acknowledged low toxicity, dithiocarbamates are known to cause a wide range of neurobehavioral effects as well as neuropathological changes in the brain. Astrocytes play a key role in normal brain physiology and in the pathology of the nervous system. This investigation studied the effects of 1.0 µM Ziram on rat hippocampal astrocytes. The thiobarbituric acid reactive substance assay performed showed a significant increase in malondialdehyde, a product of lipid peroxidation, in the Ziram-treated cells. Biochemical analysis also revealed a significant increase in the induction of 70 kDa heat shock and heme oxygenase 1 stress proteins. In addition, an increase of glutathione peroxidase (GPx) and a significant increase in oxidized glutathione (GSSG) were observed in the Ziram-treated cells. The ratio GSH to GSSG calculated from the treated cells was also decreased. Light and transmission electron microscopy supported the biochemical findings in Ziram-treated astrocytes. This data suggest that the cytotoxic effects observed with Ziram treatments may be related to the increase of oxidative stress.
Oxidative stress plays an important role in causing diabetes; however, no studies have thoroughly reported on the toxic and beneficial effects of lichen extracts in patients with diabetes mellitus (DM). This study covers a previously unrecognized effect of two well-known lichen species Cetraria islandica and Pseudevernia furfuracae in streptozotocin (STZ)-induced diabetes. In experimental design, control or diabetic rats were either untreated or treated with aqueous lichen extracts (250–500 mg/kg /day) for 2 weeks starting at 72 h after STZ injection. On day 14, animals were anaesthetized, and metabolic and biochemical parameters were appreciated between control and treatment groups. The histopathology of liver was examined using three different staining methods: hematoxylin–eosin (H&E), periodic acid Schiff (PAS), and reticulin and Sudan Black B. Our experimental data showed that increasing doses of C. islandica and P. furfuracae alone did not have any detrimental effects on studied parameters and the malondialdehyde level of liver. C. islandica extract showed positive results for antioxidant capacity compared to doses of P. furfuracae extract. However, the protective effect of C. islandica extract on diabetes-induced disorders and hepatic damages is still unclear. Moreover, unfortunately, animals subjected to DM therapy did not benefit from the usage of increasing lichen doses due to their unchanged antioxidant activity in tissues. The results obtained in present study suggested that C. islandica and P. furfuracae is safe but the power of these is limited because of intensive oxidative stress in liver of type 1 diabetic rats. It is also implied that C. islandica extract is especially suitable for different administration routes in DM animals.
The aim of this project was to study the clinical manifestations, neurobehavioral, hematobiochemical, oxidative stress, genotoxicity, and histopathological changes during acrylamide toxicity in rats. A total of 30 adult male Wistar rats were divided in 5 equal groups and received 0, 10, 15, and 20 mg/kg body weight acrylamide as oral gavage, while group 5 was micronucleus (MN) control. Functional observational battery (FOB) parameters were studied at the 28th day of post treatment. Toxicological manifestations were evident in acrylamide-treated rats from 14th day onward. FOB revealed a significant change in central nervous system, neuromuscular, and autonomic domains. The hematological changes include significant decrease in concentration of hemoglobin, total erythrocyte count, packed cell volume, and mean corpuscular volume. The biochemical parameters aspartate aminotransferases, alkaline phosphatase, and albumin showed significant increase, while the levels of serum globulin and glucose were found to decrease significantly. The MN assay revealed the significant increase in frequencies of micronuclei and number of polychromatic erythrocytes. The oxidative stress parameters revealed no significant difference as compared to control rats. Histopathological changes observed in brain include neuronal degeneration, edema, and congestion, while spinal cord revealed demyelination in low-dose group and bilateral necrosis with malacia, liquefaction of white matter, and loss of myelin from gray matter in high-dose groups. The result indicates pathological alterations in brain and spinal cord and is responsible for neurobehavioral changes in rats. The FOB changes and histopathological alterations in spinal cord are in dose dependent to acrylamide intoxication. Various toxicological effects observed in experiment direct us to focus on a deep study and evaluate the possible causes pertaining to toxicity of this chemical. It would furnish the scientists with better options that would help them to search for a median path regarding the use of this chemical and take preventive measures to save the living beings from the hidden disasters of this chemical.
In the present study, the effect of different in vitro cultures (callus, in vitro shoots) and commercially available peppercorn extract was investigated for its activity against toxic metabolite-producing strains (Escherichia coli, Pseudomonas aeroginosa, Salmonella typhi, Bacillus subtilis, Bacillus cereus, Staphylococcus aureus, and Candida albicans). These in vitro cultures were extracted with ethanol, hexane, and chloroform, and the antipathogenic activity was determined by well-diffusion method. Hexane extract of callus showed 22 mm zone of inhibition against B. cereus, 23 mm against S. aureus, while regenerated shoots and seeds have shown 24.3 and 26 mm zones of inhibition. The ethanolic extracts of regenerated Piper shoots have shown 25 mm activity against S. aureus, 21 mm against B. cereus, and 16 mm in the case of C. albicans in comparison with standard antibiotics. Peppercorn extracts in chloroform and ethanol had shown activities against B. cereus (23.6 mm) and B. subtilis (23.5 mm). During in vitro organogenesis and morphogenesis, cells and tissues produced a comparable phytochemicals profile like mother plant. Morphogenesis is critically controlled by the application of exogenous plant-growth regulators. Such addition alters the hormonal transduction pathways, and cells under in vitro conditions regenerate tissues, which are dependant on the physiological state of cells, and finally enhance the production of secondary metabolites. To the best of our knowledge, this is the first report to compare the antimicrobial potential of in vitro regenerated tissues and peppercorn with standard antibiotics. In conclusion, most of the extracts showed pronounced activities against all the pathogenic microbes. This is a preliminary work, and the minimum inhibitory concentration values needs to be further explored. Regenerated tissues of P. nigrum are a good source of biologically active metabolites for antimicrobial activities, and callus culture presented itself as a good candidate for such activities.
In this article, the genotoxic and antigenotoxic effects of methanol extract of of Cladonia foliacea (Huds.) Willd. (CME) were studied using WP2, Ames (TA1535 and TA1537), and sister chromatid exchange (SCE) test systems. The results of our studies showed that 5 µM concentration of aflatoxin B1(AFB1) changed the frequencies of SCE and malondialdehyde (MDA) levels, superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GPx) activities. When 5 and 10 µg/mL concentrations of CME was added to AFB1, the frequencies of SCE and MDA level were decreased and SOD, GSH, and GPx levels were increased. The extract CME did not show any mutagenicity on Ames (Salmonella typhimurium TA1535, TA1537) and WP2 (Escherichia coli) test systems. On the other hand, CME has antimutagenicity on the mentioned test systems. The results of this experiment have clearly shown that CME has a significant antioxidative and antigenotoxic effect, which is thought to be due to the antigenotoxic activities of antioxidant enzymes.
The purpose of the present investigation was to evaluate cadmium (Cd)-induced neurotoxicity in hippocampal tissues and beneficial effect of quercetin (QE) against neuronal damage. A total of 30 male rats were divided into 3 groups: control, Cd-treated, and Cd + QE-treated groups. After the treatment, the animals were killed and hippocampal tissues were removed for biochemical and histopathological investigation. Cd significantly increased tissue malondialdehyde (MDA) and protein carbonyl (PC) levels and also decreased superoxide dismutase (SOD) and catalase (CAT) enzyme activities in hippocampal tissue compared with the control. Administration of QE with Cd significantly decreased the levels of MDA and PC and significantly elevated the levels of antioxidant enzymes in hippocampal tissue. In the Cd-treated group, the neurons of both tissues became extensively dark and degenerated with pyknotic nuclei. The morphology of neurons in Cd + QE group was well protected, but not as neurons of the control group. The caspase-3 immunopositivity was increased in degenerating neurons of the Cd-treated group. Treatment of QE markedly reduced the immunoreactivity of degenerating neurons. The results of the present study show that QE therapy causes morphologic improvement in neurodegeneration of hippocampus after Cd exposure in rats.
Lichens are symbiotic organisms composed of fungi and algae and are very common in Turkey. Lichen secondary metabolites are mainly phenolic compounds produced by fungal partner of lichen symbiosis. Usnic acid (UA) is one of the most common lichen metabolites, and it was reported that to be effective for a wide range of pharmacological purposes including antiviral, antitumor, and antiprotozoal. However, there are limited data on the genotoxic and antioxidant effects of UA in cultured human peripheral blood cells. Therefore, the aim of this thesis study was to investigate the genetic and oxidative effects of UA in cultured human blood cells (n = 5). The UA was added into culture tubes at various concentrations (0–200 μg/ml). Chromosomal aberrations (CA) and micronuclei (MN) tests were performed for genotoxic damage influences estimation. In addition, biochemical parameters (total antioxidant capacity (TAC) and total oxidative status (TOS)) were examined to determine oxidative effects. In our in vitro test systems, it was observed that UA had no mutagenic effects on human lymphocytes. Furthermore, our results indicated that low concentrations (1 and 5 μg/ml) of UA caused increases of TAC levels in cultured human blood cells. And, the TOS levels were not changed (p > 0.05) when all the concentrations (except for 200 μg/ml) of UA were applied. In conclusion, UA can be a new resource of therapeutics as recognized in this study with their nonmutagenic and antioxidant features.
The aim of this study was to determine the antifungal effect of the essential oil obtained from Ziziphora clinopodioides L on two fungi species including Aspergillus flavus and Aspergillus parasiticus using microdilution method. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were determined for the essential oil at 10 different concentrations (i.e. 25,000, 12,500, 6250, 3125, 1562.5, 781.25, 390.625, 195.31, 97.65, and 48.82 µg/ml). Finally, the effect of the essential oil at six levels (6250, 3125, 1600, 800, 400, and 196 µg/ml) was investigated on the growth and activity of A. flavus and A. parasiticus, and also toxin production of these species in maize at 0.97 aw and 25°C after 29 days. Aflatoxin B1 (AFB1) content was assayed by enzyme linked immuno-sorbent assay technique. Results showed that essential oil of Z. clinopodioides was found more effective on A. parasiticus than A. flavus in both in vitro and in vivo conditions. Z. clinopodioides oil exhibited the same MIC value in the liquid medium against all fungal strains (48.82 µg/ml), while it showed different activity against A. flavus and A. parasiticus with MFC values of 781.25 and 390.625 µg/ml respectively. Under storage condition in maize, AFB1 production was significantly (p < 0.05) repressed at the concentration of 6250 µg/ml for A. flavus and 6250 and 3125 µg/ml for A. parasiticus. At the lower concentrations, the AFB1 production increased gradually. The results of the present study indicated that the essential oil of Z. clinopodioides had significant antifungal activity (p < 0.05); therefore, it can be used as an antifungal agent in the food and medicinal industries.
In the present work, 6 honeydew samples of known geographical and botanical origins and 11 honeybee samples were analyzed to detect possible contamination by the thermoelectric power plants in Mugla, Turkey. The contents of trace elements were determined by atomic absorption spectrometry after application of microwave digestion. The samples from the thermal power plants, which were 10–22 km away from the hives, that did not cause pollution in honeydew honeys were also analyzed. The levels of copper, cadmium (Cd), lead (Pb), zinc, manganese, iron, chromium, nickel, and aluminum were similar to the values found in other recent studies in literature. However, it was found that the contamination levels of the toxic elements such as Pb and Cd in honeybee samples measured relatively higher than that of honey samples. The study concludes that honeybees may be better bioindicators of heavy metal pollution than honey.
Complications of substances detected in poisoning deaths are important in order to observe changes in poisoning patterns and to monitor effects of preventive work. The aim of the present study was to describe the characteristics of substances investigated and detected in poisoning deaths by Adana Group Authority of the Council of Forensic Medicine, Department of Forensic Chemistry, Cukurova, Turkey, between 2007 and 2011 retrospectively. A total of 7681 examinations were performed, of which, 7% (n = 564) determined positive for at least one compound investigated. Ages of the cases ranged from 1 to 97 years (mean ± SD: 36.10 ±19.16). Carbon monoxide (CO) poisonings were found most frequently with an incidence of 27.0%, followed by prescription medications with 25.0%. Illegal drug poisonings were present in 20.0% of blood and urine samples analyzed. Pesticides, mostly endosulfan, were found in 13.0% of the 564 cases investigated. In the blood samples analyzed, methyl and ethyl alcohol were detected in 14.0% and volatile substances in 1.0%. Overall, this study has managed to contribute substantial additional information regarding the epidemiology of poisoning in Cukurova region, Southern Turkey. The results confirm other epidemiological data that indicate CO as the major cause of poisoning deaths in Turkey.
Our study aimed to determine the cardiac toxicities of T-2 toxin, a representative mycotoxin that frequently contaminates maize, cereals, and other agricultural products, harvested and stored under damp and cold conditions. Dermal exposure to T-2 toxin caused severe cardiotoxicity in experimental Wistar rats. Electrocardiography studies showed the conduction abnormalities including prolongation of the QT and corrected QT interval, shortening of the PR interval, and tachycardia. Biochemical studies also reported the toxicity of T-2 toxin. T-2 toxin induced acute cardiotoxicity in rats and characterized by significant (p < 0.05) elevation of serum troponin I, creatine kinase (CK) isoenzyme MB, CK isoenzyme NAC, and lactate dehydrogenase as compared to control rats. It is concluded that cardiotoxicity effects of T-2 toxin are thought to be due to direct action on electrocardiac potentials and biochemical changes.
The aim of the present study was to analyze the impact of environmental contamination on oxidative stress and histopathologic biomarkers in liver of the Nile tilapia, Oreochromis niloticus, collected from four sites that differ in their extent of pollution load, including heavy metals: the southeast basin (SEB), main basin (MB), and northwest basin (NWB) of Lake Mariut as well as Boughaz El-Maadiya, a channel in Lake Edku. The SEB was the less-impacted site, and thus considered as a reference. High concentrations of heavy metals (cadmium, copper, iron, lead, zinc, and manganese) were detected in fish liver at sites with anthropogenic pressure. All biomarkers, lipid peroxidation (in the MB, NWB, and Lake Edku), superoxide dismutase (in the MB and NWB), and glutathione peroxidase, and reduced glutathione (in the NWB) were found to be significantly higher compared to the reference values. Catalase, glutathione reductase, and glucose-6-phosphate dehydrogenase showed a varied response and displayed significantly lower activities in the polluted sites. Certain hepatic lesions, detected microscopically, were stimulated in fish from the MB and NWB, reflecting the high contamination of these areas. These included foci of necrosis, melanomacrophage infiltration, congestion, nuclear pyknosis, and extensive vacuolation corresponding to relatively higher lipid content. Overall, our results suggest that the selected biomarkers are useful for the assessment of pollution impacts in natural aquatic environments influenced by multiple pollution sources. The existence of chronic background pollution of the test sites implies that the observed biomarker responses cannot be solely attributed to heavy metals.
This study was designed to estimate protective effects of silymarin on acetaminophen (N-acetyl-p-aminophenol, paracetamol; APAP)-induced hepatotoxicity and nephrotoxicity in mice. Treatment of mice with overdose of APAP resulted in the elevation of aspartate aminotransferase (AST), alanine transaminase (ALT), blood urea nitrogen (BUN), and serum creatinine (SCr) levels in serum, liver, and kidney nitric oxide (NO) levels and significant histological changes including decreased body weight, swelling of hepatocytes, cell infiltration, dilatation and congestion, necrosis and apoptosis in liver, and dilatation of Bowman’s capsular space and glomerular capillaries, pale-stained tubules epithelium, cell infiltration, and apoptosis in kidney. Posttreatment with silymarin 1 h after APAP injectionfor 7 days, however, significantly normalized the body weight, histological damage, serum ALT, AST, BUN, SCr, and tissue NO levels. Our observation suggested that silymarin ameliorated the toxic effects of APAP-induced hepatotoxicity and nephrotoxicity in mice. The protective role of silymarin against APAP-induced damages might result from its antioxidative and anti-inflammatory effects.
Chronic long-term exposure to high levels of fluoride leads to fluorosis, manifested by skeletal fluorosis and damage to internal organs, including kidneys, liver, parathyroid glands, and brain. Excess fluoride can also cause DNA damage, trigger apoptosis, and change cell cycle. The effect of fluoride may be exacerbated by lead (Pb), a potent inhibitor of many enzymes and a factor causing apoptosis, still present in the environment in excessive amounts. Therefore, in this study, we investigated the effects of sodium fluoride (NaF) and/or lead acetate (PbAc) on development of apoptosis, cell vitality, and proliferation in the liver cell line HepG2. We examined hepatocytes from the liver cell line HepG2, incubated for 48 h with NaF, PbAc, and their mixture (NaF + PbAc), and used for measuring apoptosis, index of proliferation, and vitality of cells. Incubation of the hepatocytes with NaF or PbAc increased apoptosis, more when fluoride and Pb were used simultaneously. Vitality of the cells depended on the compound used and its concentration. Proliferation slightly increased and then decreased in a high fluoride environment; it decreased significantly after addition of Pb in a dose-dependent manner. When used together, fluoride inhibited the decreasing effect of Pb on cell proliferation.
In the present study, concentrations of arsenic (As), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), manganese (Mn), nickel (Ni), lead (Pb), and zinc (Zn) were measured in the muscle, gill, and gonads of the pelagic fish species Trachurus mediterraneus, Engraulis encrasicolus ponticus, and Sprattus sprattus that are important both commercially and for the ecosystems in the Black Sea. The samples were collected during 2011. The metals were determined using inductively coupled plasma mass spectrometry (ICP-MS) following an acid digestion. The highest concentrations of As, Cd, Co, Cr, Cu, Pb, and Zn were found in E. encrasicolus ponticus, whereas the greatest concentrations of Ni were found in T. mediterraneus and Mn in S. sprattus. Results showed that average metal concentrations in the tissues of T. mediterraneus, E. encrasicolus ponticus, and S. sprattus decreased in the order gill > gonad > muscle, gonad > gill > muscle, and gill > gonad > muscle, respectively, for the three species. When metal concentrations of fish tissues were compared between fish gender, there were only statistical differences in the gonads of the studied fish species (p < 0.05). The present study demonstrated that the metals have different correlations with condition factor (CF) and gonadosomatic index (GSI) of the fish species. Cr showed statistically important positive correlation to the GSI in male T. mediterraneus. Co showed statistically important positive correlation to CF in female E. encrasicolus ponticus, and also Co and Cd showed correlation to CF in male T. mediterraneus. Cd concentrations in the muscle tissues of the fish species were above the maximum acceptable concentration for human consumption.
The aim of this research was to develop a low price and environmentally friendly adsorbent with abundant of source to remove methylene blue (MB) from water samples. Sawdust solid-phase extraction coupled with high-performance liquid chromatography was used for the extraction and determination of MB. In this study, an experimental data-based artificial neural network model is constructed to describe the performance of sawdust solid-phase extraction method for various operating conditions. The pH, time, amount of sawdust, and temperature were the input variables, while the percentage of extraction of MB was the output. The optimum operating condition was then determined by genetic algorithm method. The optimized conditions were obtained as follows: 11.5, 22.0 min, 0.3 g, and 26.0°C for pH of the solution, extraction time, amount of adsorbent, and temperature, respectively. Under these optimum conditions, the detection limit and relative standard deviation were 0.067 μg L-1 and <2.4%, respectively. The Langmuir and Freundlich adsorption models were applied to describe the isotherm constant and for the removal and determination of MB from water samples.
Heavy metals are being increasingly released into the natural waters from geological and anthropogenic sources. The distributions of several heavy metals such as cadmium (Cd) and lead (Pb) were investigated in muscle and liver of three different fish species seasonally collected from Caspian Sea (autumn 2011–summer 2012). The concentrations of all metals were lower in flesh than those recorded in liver due to their physiological roles. The target hazard quotient (THQ) index for fish was calculated. Estimation of THQ calculations for the contaminated fish consumption was calculated to evaluate the effect of pollution on health. Total metal THQ values of Pb and Cd for adults were 0.05 and 0.04 in Anzali and Noshahr, respectively, and for children were 0.08 and 0.05 in Anzali and Noshahr, respectively.
Aim: To evaluate the antibacterial effect of curcumin with the minimum inhibitory concentration (MIC) method in standard bacterial strains. Methods: The in vitro antibacterial activity of curcumin was evaluated against methicillin-sensitive Staphylococcus aureus (MSSA) (ATCC 29213), methicillin-resistant Staphylococcus aureus (MRSA) (ATCC 43300), Enterococcus faecalis (ATCC 29212), Bacillus subtilis (ATCC 6633), Pseudomonas aeruginosa (ATCC 27853), Escherichia coli (ATCC 25922) and Klebsiella pneumoniae (ATCC 700603) using the macrodilution broth susceptibility test method. After incubation in tubes, the antibacterial activity of curcumin was detected by a lack of turbidity, which indicated the inhibition of bacterial growth. The concentration in the tube with the highest dilution showing no turbidity was defined as the MIC. Results: The curcumin MIC values were 175 µg/ml, 129 µg/ml, 219 µg/ml, 217 µg/ml, 163 µg/ml, 293 µg/ml and 216 µg/ml against P. aeruginosa, B. subtilis, MSSA, MRSA, E. coli, E. faecalis and K. Pneumonia, respectively. Conclusion: This study revealed antibacterial effects of curcumin against standard bacterial strains in high concentrations. Animal experiments have demonstrated that curcumin applied at high doses has strong antibacterial activity. There is a need for further in vivo studies to shed light on antibacterial effects of curcumin with high concentrations.
Stroke is one of the major reasons of death in the United States and related to adult disability. Despite aggressive research, the treatment approaches of stroke still remains a major clinical problem. Intravenous immunoglobulin (IVIg) is a polyspecific Ig G preparation obtained from plasma of several thousand healthy people (donors). IVIg is an important treatment approach and used for several disorders. The aim of this study was to investigate the potentially beneficial effects of IVIg therapy in experimentally induced ischemia in middle cerebral artery occlusion (MCAo) models of rats. A total of 30 adult male Sprague Dawley rats were used. The rats were divided into two equal groups, each consisting of 15 randomly selected rats: control group (n = 15) and IVIg group (n = 15). Intraluminal filament method was used for establishment of cerebral ischemia. Intraluminal filament was withdrawn after 2 h of MCAo and reperfusion started again and passed to therapeutic stages for all the groups. Physiologic saline solution of 0.5 ml/kg was administered to the control group and 400 mg/kg IVIg was given to the IVIg group rats intravenously. In neurological evaluation, the worst score was determined as 3 and the best score as 0. After routine process, the brain tissue was prepared histopathological investigation. The IVIg group showed significantly better recovery with respect to the control group by neurological examination. The observation of specimens obtained from IVIg groups showed that findings correlate with grade 1 and -2 histopathologically. Nevertheless, ischemic amendments were observed to comply with grade 3 in ischemic areas in control group. IVIg therapy can be used in the treatment of ischemic stroke patients.
Mobile phones are extensively used throughout the world. There is a growing concern about the possible public health hazards posed by electromagnetic radiation emitted from mobile phones. Potential health risk applies particularly to the most intensive mobile phone users—typically, young people. The aim of this study was to investigate the effects of mobile phone exposure to the testes, by assessing the histopathological and biochemical changes in the testicular germ cells of rats during pubertal development. A total of 12 male Sprague Dawley rats were used. The study group (n = 6) was exposed to a mobile phone for 1 h a day for 45 days, while the control group (n = 6) remained unexposed. The testes were processed with routine paraffin histology and sectioned. They were stained with hematoxylin–eosin, caspase 3, and Ki-67 and then photographed. No changes were observed between the groups (p > 0.05). The interstitial connective tissue and cells of the exposed group were of normal morphology. No abnormalities in the histological appearance of the seminiferous tubules, including the spermatogenic cycle stage, were observed. Our study demonstrated that mobile phones with a low specific absorption rate have no harmful effects on pubertal rat testicles.
Human exposure to monocrotophos, an organophosphate pesticide, could occur due to its high use in agriculture to protect crops. Recently, we found that postlactational exposure to monocrotophos impaired cholinergic mechanisms in young rats and such changes persisted even after withdrawal of monocrotophos exposure. In continuation to this, the effect of monocrotophos on noncholinergic targets and role of oxidative stress in its neurotoxicity has been studied. Exposure of rats from postnatal day (PD)22 to PD49 to monocrotophos (0.50 or 1.0 mg kg-1 body weight, perorally) significantly impaired motor activity and motor coordination on PD50 as compared to controls. A significant decrease in the binding of 3H-spiperone to striatal membrane (26%, p < 0.01; 30%, p < 0.05) in rats exposed to monocrotophos at both the doses and increase in the binding of 3H-ketanserin to frontocortical membrane (14%, p > 0.05; 37%, p < 0.05) in those exposed at a higher dose, respectively, was observed on PD50 compared with the controls. Alterations in the binding persisted even after withdrawal of monocrotophos exposure on PD65. Increased oxidative stress in brain regions following exposure of rats to monocrotophos was also observed on PD50 that persisted 15 days after withdrawal of exposure on PD65. The results suggest that monocrotophos exerts its neurobehavioral toxicity by affecting noncholinergic functions involving dopaminergic and serotonergic systems associated with enhanced oxidative stress. The results also exhibit vulnerability of developing brain to monocrotophos as most of the changes persisted even after withdrawal of its exposure.
An 8-week trial was conducted to investigate the effect of ambient copper (Cu) on growth performance, physiological characteristics and stress resistance of Caspian roach, Rutilus rutilus caspicus. Fish were exposed to 0 (control), 0.02, 0.04 and 0.06 ppm Cu, and their food intake and growth performance were fortnightly recorded. Also, serum cortisol, glucose, alanine aminotransferase (ALT) and sodium (Na) levels were determined after 2 and 8 weeks exposure to ambient Cu. At the end of trial, serum total protein, albumin, globulin and albumin–globulin ratio (A:G) levels, whole body proximate composition and stress tolerance of the fish were measured. Results showed that Cu exposure resulted in a significant suppression in food intake after 2 weeks, which was eliminated after 4 weeks in 0.02 ppm groups and after 6 weeks in 0.04 and 0.06 ppm groups. Cu exposure brought about an inferior growth that recovered in line with the experiment progression, following a dose-dependent manner. Cu-exposed fish showed a dose-dependent increase in serum cortisol, glucose and ALT as well as decrease in serum Na, after 2 weeks. These parameters showed a full recovery in 0.02 ppm group and a partial recovery in 0.04 and 0.06 ppm groups, at the 8th week. Significant suppression in serum total protein, albumin, globulin and A:G levels and whole body dry matter, lipid and protein levels as well as stress resistance was observed in 0.04 and 0.06 ppm groups. It is concluded that Cu exposure could adversely affect growth performance, physiological characteristics and stress resistance of Caspian roach, which might affect its ecological features.
The objective of the present study was to study the effect of graded doses of citrinin (CIT) on apoptosis and oxidative stress in male Wistar rats till F1 generation. The animals were divided into four groups comprising 25 males and 25 females each, that is, group I: 1 ppm CIT; group II: 3 ppm CIT; group III: 5 ppm CIT; and group IV was kept as a control. The male and female animals of all the groups were kept separately and were fed basal rations containing the above-mentioned concentrations of CIT for 10 weeks. After 10 weeks, male and female animals of respective groups were kept for mating (one male/two females). After getting 10 pregnant females, the males were killed. These 10 pregnant females were allowed to give birth to young ones (F1 generation) naturally which were fed CIT in the above-mentioned doses till the age of 6 weeks and then were killed. Apoptosis was analysed in kidneys, liver and testes by DNA ladder pattern, terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end-labelling assay and Bcl-2/Bax ratio. Besides, tissue oxidative stress was also analysed. It was concluded in the present study that CIT induces its toxic effects till F1 generation, and apoptosis and oxidative stress both play a very important role in toxicity. The effect of CIT was observed in a dose-dependent manner. However, in kidneys, both the mechanisms (apoptosis and oxidative stress) play their role in inflicting renal damage, while in liver only reactive oxygen species play a major role. Finally, the CIT toxicity did not lead to apoptosis and oxidative stress in male gonads till F1 generation.
Concentrations of 11 metals (cadmium, zinc, copper (Cu), vanadium (V), lead, magnesium (Mg), manganese, aluminum, iron (Fe), chromium (Cr), and nickel), and one metalloid (arsenic (As)) were measured in sediment, common reed (Phragmites australis), algae (Spirogyra sp.), and blood worm (Chironomus sp.) tissues of samples collected from the Shoor river. Samples were dried, acid digested, and the concentrations of metals were measured using inductively coupled plasma–optical emission spectrometer. A higher concentration of heavy metals was accumulated in Spirogyra and Chironomids than sediment and common reed. The highest rate of accumulation was found for Mg, V, Fe, As, Cu, and Cr. Spirogyra and Chironomids are capable of accumulating and thereby removing metals from polluted water bodies and are suitable for biomonitoring purposes.
Arsenic exposure through drinking water causes oxidative stress and tissue damage in the kidney and brain. Curcumin (CUR) is a good antioxidant with limited clinical application because of its hydrophobic nature and limited bioavailability, which can be overcome by the encapsulation of CUR with nanoparticles (NPs). The present study investigates the therapeutic efficacy of free CUR and NP-encapsulated CUR (CUR-NP) against sodium arsenite-induced renal and neuronal oxidative damage in rat. The CUR-NP prepared by emulsion technique and particle size ranged between 120 and 140 nm, with the mean particle size being 130.8 nm. Rats were divided into five groups (groups 1–5) with six animals in each group. Group 1 served as control. Group 2 rats were exposed to sodium arsenite (25 ppm) daily through drinking water for 42 days. Groups 3, 4, and 5 were treated with arsenic as in Group 2; however, these animals were also administered with empty NPs, CUR (100 mg/kg body weight), and CUR-NP (100 mg/kg), respectively, by oral gavage during the last 14 days of arsenic exposure. Arsenic exposure significantly increased serum urea nitrogen and creatinine levels. Arsenic increased lipid peroxidation (LPO), reduced glutathione content and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were depleted significantly in both kidney and brain. Treatment with free CUR and CUR-NP decreased the LPO and increased the enzymatic and nonenzymatic antioxidant system in kidney and brain. Histopathological examination showed that kidney and brain injury mediated by arsenic was ameliorated by treatment. However, the amelioration percentage indicates that CUR-NP had marked therapeutic effect on arsenic-induced oxidative damage in kidney and brain tissues.
This study investigates the preventive effect of caffeic acid phenethyl ester (CAPE) on pancreatic damage induced by vancomycin (VCM) in rats. Rats were equally divided into three groups: group I (control), group II (only VCM-treated group) and group III (VCM + CAPE-treated groups). VCM was intraperitoneally administered at a dose of 200 mg kg-1 twice daily for 7 days. CAPE was administered orally at 10 µM mL-1 kg-1 dose once daily for 7 days. The first dose of CAPE administration was performed 24 h prior to VCM injection. Blood and pancreas tissue samples were removed and collected after the study. Serum alkaline phosphatase (ALP), amylase, -glutamyl transferase (GGT) and lipase activities were determined. Pancreas tissue samples were evaluated with the light microscope. Group II significantly increased serum ALP, amylase, GGT and lipase activities when compared with the control group. Group III significantly decreased serum ALP, amylase, GGT and lipase activities when compared with group II. In histopathological examination, it has been observed that there was a significant pancreatic damage in group II. CAPE exerted prominent structural protection against VCM-induced pancreatic damage and this effect was statistically significant. CAPE caused a marked reduction in the extent of pancreatic damage. We have concluded that it may play an important role in the VCM-induced pancreatic damage and reduce the pancreatic damage both at the biochemical and histopathological aspects.
The protection afforded by melatonin (MLT) against diazinon (DZN)-induced micronucleus formation, an index of DNA damage, in human blood lymphocytes was investigated. Whole blood samples were collected from five volunteers and were incubated with MLT at different concentrations (100, 200, 300, and 400 µM final concentration) for 1 h. The samples were then incubated with 750 µM DZN for 1 h. Subsequently, the lymphocytes were cultured with a mitogenic stimulant to evaluate micronucleus formation in cytokinesis-blocked binucleated cells. The incubation of lymphocytes with DZN induces additional genotoxicity. Pretreatment with MLT at these doses significantly reduced the micronucleus frequency in cultured lymphocytes (p < 0.05–p < 0.0001). The maximum decrease in the frequency of micronuclei was observed at 400 µM of MLT, which caused a reduction of 87%. MLT also exhibited an excellent and dose-dependent radical-scavenging activity against 1,1-diphenyl-2-picrylhydrazyl free radicals. Our study revealed that MLT has a potent antigenotoxic effect against DZN-induced DNA damage, which may be due to the scavenging of free radicals and increased antioxidant status. Because MLT is a natural compound and is considered safe, it can be used as a supplement to protect people exposed to chemical or environmental hazards.
The antitumor activity of various six fractions of Launaea procumbens were studied using the potato disk bioassay technique. Three concentrations (10, 100, and 1000 ppm) of all these six fractions were used for characterization of antitumor activity. Among these fractions, methanolic fraction exhibited significant inhibition of crown gall tumors caused by Agrobacterium tumefaciens followed by butanolic fraction. These results revealed that methanolic and butanolic fractions contain bioactive constituents responsible for inhibition of tumor. Further purification and characterization are in progress in our laboratory.
The long-term clinical use of methotrexate (MTX) is restricted due to its severe intestinal toxicity. The protective effect of ginger or propolis on the toxicity induced by MTX is relatively less understood, so the possible protective effect of ginger or propolis, used separately, was investigated. A total of 60 male albino rats were divided into six groups as follows: (1) control group; (2) ginger group; (3) propolis group; (4) MTX group; (5) ginger + MTX group; and (6) propolis + MTX group. The present results show that MTX caused ileum injury, including shortening and fusion of the villi, inflammatory cell infiltration and goblet cell depletion. Administration of ginger or propolis ameliorated the MTX-induced ileum injury as shown by histological, immunohistochemical and ultrastructural investigations and statistical analysis. This is revealed by intact villi, which shows marked increase in brown colouration of proliferating cell nuclear antigen positive nuclei in the crypts region, improvement in the number of goblet cells and brush border length of ileum. The current results conclude the efficacy and safety of ginger and propolis, which may be due to their antioxidant properties.
The purpose of the present study was to investigate the oxidative damage and apoptosis induced by aflatoxin B1 (AFB1) in spleen of broilers. A total of 200 one-day-old avian male broilers were randomly divided into 4 equal groups of 50 each and were fed for 21 days as follows: a control diet and three AFB1 diets containing 0.15, 0.3, and 0.6 mg AFB1/kg diet. Consumption of AFB1 diets induced oxidative stress in the spleen of chicken as evidenced by reduced glutathione peroxidase, glutathione reductase, and catalase activities, decreased glutathione contents, and increased malondialdehyde contents in explaining the pathogenesis. Flow cytometer method and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling assay revealed that the apoptotic splenocytes were increased in AFB1 groups. The results suggest that AFB1 induced excessive apoptosis of splenic lymphocytes, which is correlated with increased oxidative stress. The present results may be helpful for explaining the pathogenesis of AFB1-induced immunosuppression.
Saffron (Crocus sativus) is a widely used food additive for its color and taste. Crocin and safranal are two main components of this plant. Numerous studies are underway to introduce saffron and its active ingredients as pharmacological agents. Safety assessments of these compounds are important parts of this endeavor. In this study, the effects of crocin and safranal administrations during embryogenesis have been investigated in mice. A total of 75 BALB/c pregnant mice were divided into six experimental and control groups. Four experimental groups received intraperitoneal injection of crocin (200 mg/kg or 600 mg/kg) daily or safranal (0.075 ml/kg or 0.225 ml/kg) on gestational days (GDs) 6 to 15. Control groups received normal saline or paraffin as solvents of crocin and safranal. Dams were dissected on GD18 and embryos were collected. Routine maternal and fetal parameters were recorded. Macroscopic observation of external malformations was also performed. Fetuses were then selected for double skeletal staining with alizarin red and alcian blue. All experimental groups caused significant decrease in length and weight of fetuses when compared with the control groups and revealed malformations such as minor skeletal malformations, mandible and calvaria malformations, and growth retardation. Minor skeletal malformations were the most commonly observed abnormality, which were statistically significant when compared with the control groups (p < 0.05). The severities of malformations were comparable in the crocin- and safranal-treated groups. This study suggests that crocin or safranal can induce embryonic malformations when administered in pregnant mice. Due to the wide use of saffron, further elaborate studies to understand the malformation mechanisms of these ingredients are recommended.
Background: The aim of this study was to establish the protective effect of caffeic acid phenethyl ester (CAPE) against the ifosfamide (IFOS)-induced central neurotoxicity in rats and to determine the changes in oxidant–antioxidant status of brain tissue. Method: A total of 35 Wistar rats (aged 7-12 days) were used in the experiments. The study comprised of five groups. Control untreated rats (n = 7) belonged to group 1; group 2 was given intraperitoneal (IP) injection of CAPE alone (10 µmol/kg; n = 7); group 3 was treated with single IP injection of IFOS (500 mg/kg; n = 7); group 4 was treated for 2 days with IP administration of CAPE (10 µmol/kg) beginning from one day before single IP injection of IFOS (n = 7); and group 5 was treated with saline and 10% ethanol. At the 24th hour of IFOS treatment, brain tissues were removed for analysis. Results: The brain catalase activity was lower in IFOS group than the other groups (p < 0.05). The levels of malondialdehyde (MDA) and protein carbonyl content in brain tissue were higher in IFOS group than the control, CAPE, ethanol, and IFOS + CAPE groups (p < 0.05). There was no significant difference between MDA and protein carbonyl content of control, CAPE, ethanol, and IFOS + CAPE groups. Immunohistochemistry showed marked activation of caspase 3 in the IFOS group at 24 h after treatment. Conclusion: This study revealed that pretreatment with CAPE might protect brain tissue against IFOS-induced central neurotoxicity. CAPE could be an effective course of therapy to enhance therapeutic efficacy and to lessen IFOS toxicity in clinical chemotherapy.
In the recent years, there has been a growing interest in monitoring heavy metal contamination of spices/herbs. Spices and herbs are sources of many bioactive compounds that can improve the tastes of food as well as influence digestion and metabolism processes. In the present study, the levels of some essential and toxic elements such as iron (Fe), zinc (Zn), copper (Cu), chromium (Cr), manganese (Mn), cobalt (Co), nickel (Ni), lead (Pb), and cadmium (Cd), present in common spices/herbs that were purchased from the local market in Saudi Arabia, were analyzed by atomic absorption spectroscopy after digestion with nitric acid/hydrogen peroxide mixture. Samples from the following spices/herbs were used: turmeric, cloves, black pepper, red pepper, cumin, legume, cinnamon, abazir, white pepper, ginger, and coriander. The concentration ranges for the studied elements were found as 48.8–231, 4.7–19.4, 2.5–10.5, below detection level (BDL)–1.0, 8.8–490, 1.0–2.6, and BDL–3.7 µg g-1 for Fe, Zn, Cu, Cr, Mn, Ni, and Pb, respectively, while Cd and Co levels were below the detection limit. Consumers of these spices/herbs would not be exposed to any risk associated with the daily intake of 10 g of spices per day as far as metals Fe, Zn, Cu, Cr, Mn, Ni, and Pb are concerned.
Infertility is becoming a health problem, which has increased mainly in megacities, and several studies have shown its association with environmental pollution. Air pollution has been linked to alterations in sperm parameters, both in humans and animal models. In male humans, it has been associated with reduced semen quality and DNA alterations. Vanadium is a transition element that has increased in recent decades as a component of air suspended matter and has been associated with reprotoxic effects in animal models. Few are the mechanisms described by which the vanadium produces these effects, and cytoskeleton interaction is a possibility. We reported immunohistochemical changes in actin testicular cytoskeleton in a vanadium inhalation experimental mice model. Our findings show that exposure to vanadium pentoxide (0.02 M) results in actin decrease in testicular cells from 3–12 weeks exposure time; this effect was statistically significant and exposure time dependent. Actin cytoskeleton damage is a mechanism that could explain vanadium reprotoxic effects and its association with impaired fertility.
Boldenone (BOL) is a derivative of the testosterone that has dual effects on humans, both directly and indirectly; directly as injection to build muscles and indirectly as through consuming meat of animals that where treated with BOL. However, the action of these steroids on different body organs structures is still unclear; therefore, the aim of the present study was to investigate the effect of the intramuscular injection of BOL undecylenate on the different organ structures. A total of 10 adult New Zealand rabbits were divided into two main groups, the first group was the control group, which includes animals that were injected intramuscularly with olive oil and the second group included animals that received two intramuscular injections of 5 mg/kg body weight BOL dissected after 6 weeks. Our results showed that intramuscular injection of rabbits with BOL showed hypertrophy in both skeletal and cardiac muscles, disturbances of the hepatocytes radially arranged cords with multifocal hepatocellular vacuolations in the liver, glomerulus mass reduction with multifocal glomerular injury in the kidney, disturbances of the cycle of spermatogenesis in the testes. In conclusion, using BOL, while preparing for a young bodybuilding contest, may cause an alteration in the histological structure of most of the body organs; these findings suggested that especially young people who misuse anablic androgenic steroids should be careful if they want to use such steroids to enhance their strength and endurance.
The effects of fipronil and fluoride co-exposure were investigated on antioxidant status of buffalo calves. A total of 24 healthy male buffalo calves divided into 4 groups were treated for 98 consecutive days. Group I, receiving no treatment, served as the control. Animals of groups II and III were orally administered with fipronil at the dosage of 0.5 mg/kg/day and sodium fluoride (NaF) at the dosage of 6.67 mg/kg/day, respectively, for 98 days. Group IV was coadministered with fipronil and NaF at the same dosages as groups II and III. Administration of fipronil alone produced significant elevation in lipid peroxidation (LPO) and decrease in the levels of nonenzymatic antioxidant glutathione (GSH). However, it did not produce any significant effect on the activities of enzymatic antioxidants including glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD). NaF exposure led to enhanced oxidative stress as shown by significant increase in the LPO and SOD activities while GPx and CAT activities and GSH levels were significantly decreased. Co-exposure to fipronil and NaF showed additive effects on LPO, GPx activity, and GSH levels.
Nicotiana plumbignifolia (Linn) is used as folk medicine in the treatment of liver dysfunction in Pakistan. The present study was designed to investigate the hepatoprotective role of N. plumbignifolia methanolice extract (NPME) against carbon tetrachloride (CCl4)-induced oxidative damage in liver of chicks. Methanolic extract of N. plumbignifolia was obtained and was further evaluated as a hepatoprotective agent against CCl4-induced oxidative damage in liver of chicks. For this study, 60-day-old 50 male chicks were divided into five groups. Chicks of group 1 (control) had free access to food and water. Group II received 1 mL/kg of CCl4 (30% in olive oil v/v) via the intraperitoneal route thrice a week for 4 weeks. Group III received 100 mg/kg body weight (b.w.) of silymarin via gavage after 48 h of CCl4 treatment, whereas group IV were given 200 mg/kg b.w. NPME after 48 h of CCl4 treatment. Hepatoprotective activity was assessed by measuring the activities of the antioxidant enzymes: catalase, peroxidase, superoxide dismutase, glutathione peroxidase, glutathione reductase, and lipid peroxidation (thiobarbituric acid reactive substances (TBARS)). Serum was analyzed for various biochemical parameters. The results revealed that CCl4 induced oxidative stress as evidenced by the significant decrease in the activity levels of antioxidant enzymes, while an increase in the levels of TBARS in liver samples is compared with the control group. Serum levels lactate dehydrogenase, triglycerides, total cholesterol, and low-density lipoprotein was elevated while reducing high-density lipoprotein compared to controls. Cotreatment of NPME treatment reversed these alterations, which seems likely that NPME can protect the liver tissues against CCl4-mediated oxidative damage.
The purpose of this study is to follow-up the distribution, lethality percentile doses (LDs) and bioaccumulation of aluminium oxide nanoparticles (Al2O3-NPs, average diameter 9.83 ± 1.61 nm) in some tissues of male albino rats, and to evaluate its genotoxicity to the brain tissues, during acute and sublethal experiments. The LDs of Al2O3-NPs, including median lethal dose (LD50), were estimated after intraperitoneal injection. The computed LD50 at 24 and 48 h were 15.10 and 12.88 g/kg body weight (b.w.), respectively. For acute experiments, the bioaccumulation of aluminium (Al) in the brain, liver, kidneys, intestine and spleen was estimated after 48 h of injection with a single acute dose (3.9, 6.4 and 8.5 g/kg b.w.), while for sublethal experiments it was after 1, 3, 7, 14 and 28 days of injection with 1.3 g/kg b.w. once in 2 days. Multi-way analysis of variance affirmed that Al uptake, in acute experiments, was significantly affected by the injected doses, organs (brain, liver, kidneys, intestine and spleen) and their interactions, while for sublethal experiments an altogether effect based on time (1, 3, 7, 14, 28 days), doses (0 and 1.3 g), organs and their interactions was reported. In addition, Al accumulated in the brain, liver, kidney, intestine and spleen of rats administered with Al2O3-NPs were significantly higher than the corresponding controls, during acute and sublethal experiments. The uptake of Al by the spleen of rats injected with acute doses was greater than that accumulated by kidney>brain>intestine>liver, whereas the brain of rats injected with sublethal dose accumulated lesser amount of Al followed by the kidney<intestine<spleen<liver. Bioaccumulation of Al, in all studied tissues, was positively correlated with the injected doses (in acute term) and the experimental periods (in sublethal term). In the acute and sublethal experiments, comet assay parameters such as the tail intensity (i.e. DNA percentage), tail extent moment and olive tail moment were estimated using a single cell gel electrophoresis/comet assay. The results showed significant increase in DNA percentage damage in the brain cells. The obtained results indicate that bioaccumulation of Al was associated with significantly increased levels of comet parameters that depended on the doses and the experimental periods. In conclusion, Al has a high affinity to get accumulated in tissues to a level that is able to induce genotoxicity. Therefore, bioaccumulation is time, dose and organ dependant.
Toxic metals such as lead and cadmium are among the pollutants that are created by the metal production factories and disseminated in the nature. In order to study the quantity of cadmium pollution in the environment of the metal production factories, 50 saplings of the spruce species at the peripheries of the metal production factories were examined and the samples of the leaves, roots, and stems of saplings planted around the factory and the soil of the environment of the factory were studied to investigate pollution with cadmium. They were compared to the soil and saplings of the spruce trees planted outside the factory as observer region. The results showed that the quantity of pollution in the leaves, stems, and roots of the trees planted inside the factory environment were estimated at 1.1, 1.5, and 2.5 mg/kg, respectively, and this indicated a significant difference with the observer region (p < 0.05). The quantity of cadmium in the soil of the peripheries of the metal production factory was estimated at 6.8 mg/kg in the depth of 0–10 cm beneath the level of the soil. The length of roots in the saplings planted around the factory of metal production stood at 11 and 14.5 cm in the observer region which had a significant difference with the observer region (p < 0.05). The quantity of soil resources and spruce species’ pollution with cadmium in the region has been influenced by the production processes in the factory.
This study aimed to find out the effect of plant growth-promoting rhizobacteria (PGPR; Azospirillum brasilense and Azotobacter vinelandii) either alone or in combination with different doses of nitrogen and phosphate fertilizers on growth, seed yield, and oil quality of Brassica carinata (L.) cv. Peela Raya. PGPR were applied as seed inoculation at 106 cells/mL-1 so that the number of bacterial cells per seed was 2.6 x 105 cells/seed. The chemical fertilizers, namely, urea and diammonium phosphate (DAP) were applied in different doses (full dose (urea 160 kg ha-1 + DAP 180 kg ha-1), half dose (urea 80 kg ha-1 + DAP 90 kg ha-1), and quarter dose (urea 40 kg ha-1 + DAP 45 kg ha-1). The chemical fertilizers at full and half dose significantly increased the chlorophyll, carotenoids, and protein content of leaves and the seed yield (in kilogram per hectare) but had no effect on the oil content of seed. The erucic acid (C22:1) content present in the seed was increased. Azospirillum performed better than Azotobacter and its effect was at par with full dose of chemical fertilizers (CFF) for pigments and protein content of leaves when inoculated in the presence of half dose of chemical fertilizers (SPH). The seed yield and seed size were greater. Supplementing Azospirillum with SPH assisted Azospirillum to augment the growth and yield, reduced the erucic acid (C22:1) and glucosinolates contents, and increased the unsaturation in seed oil. It is inferred that A. brasilense could be applied as an efficient bioinoculant for enhancing the growth, seed yield, and oil quality of Ethiopian mustard at low fertilizer costs and sustainable ways.
Boldenone (BOL) is an androgenic steroid that improves the growth and food conversion in food-producing animals. In most countries worldwide, this anabolic steroid is forbidden for human uses and meat production as it was developed for veterinary use. Recently, BOL is used by bodybuilders in both off season and pre-contest, where it is well known for increasing vascularity while preparing for a bodybuilding contest. The present study was designed to investigate the physiological and biochemical changes in rabbits after injection with the growth promoter BOL. A total of 32 adult New Zealand rabbits were divided into four groups, where the control group includes animals that were injected intramuscularly with olive oil and dissected after 3 weeks. The remaining three experimental groups included animals that received one, two and three intramuscular injections of 5 mg/kg body weight BOL, respectively, and were dissected after 3, 6 and 9 weeks, respectively. The animals from practice appeared healthy and did not show clinical signs of disease and none of the rabbits died during the experimental period. Serum total protein, globulin, alanine aminotransferase, asparate aminotransferase, urea, creatinine, testosterone, luteinizing hormone and follicle-stimulating hormone levels were significantly increased while serum direct bilirubin, albumin and albumin/globulin ratio were significantly decreased (p < 0.05) after one, two and three intramuscular injections of BOL as compared to their relative values in the control group. These findings explain the common phenomena in athletes and bodybuilders who suffer from infertility, renal and hepatic alterations following injection with some drugs as steroids (BOL) to build muscles.
The aim of this study was to investigate whether pomegranate juice (PJ) consumption has an ameliorating effect on carbon tetrachloride (CCl4)-induced sperm damages and testicular apoptosis associated with the oxidative stress in male rats. The study comprised of four groups (groups 1–4). Group 1 received olive oil + distilled water daily; group 2 was treated with 5 ml/kg PJ + olive oil daily; group 3 was treated with 0.25 ml/kg CCl4 dissolved in olive oil, weekly + distilled water daily; and group 4 received weekly CCl4 + daily PJ. All administrations were performed by gavage and maintained for 10 weeks. CCl4 administration caused significant decreases in body and reproductive organ weights, sperm motility, concentration and testicular catalase activity, significant increases in malondialdehyde (MDA) level, and abnormal sperm rate and apoptotic index along with some histopathological damages when compared with the control group. However, significant ameliorations were observed in absolute weights of testis and epididymis, all sperm quality parameters, MDA level, apoptotic index, and testicular histopathological structure following the administration of CCl4 together with PJ when compared with group given CCl4 only. In conclusion, PJ consumption ameliorates the CCl4-induced damages in male reproductive organs and cells by decreasing the lipid peroxidation.
Objectives: Prolidase is a member of the matrix metalloproteinase family. It plays a vital role in collagen turnover, matrix remodeling, and cell growth. Reactive oxygen species (ROS) have been implicated in the pathogenesis of various diseases, including cancers. Oxidative stress can cause tumor angiogenesis and may be carcinogenic. However, the relationship between antioxidant capacity and various cancers has been researched in several clinical trials. In our study, we aimed to identify serum prolidase activity, oxidative stress, and antioxidant enzyme levels in patients with renal tumors and to evaluate their relationships with each other.Materials and Methods: A total of 37 male patients with renal cell cancer and with a mean age of 56.28 ± 3.1 were included in the study. The control group comprising 36 male patients (mean age 56.31 ± 2.9) was randomly selected among the volunteers. Serum samples for measurement of superoxide dismutase (SOD), glutathione peroxidase (GSHPx), glutathione-S-transferase (GST), malondialdehyde (MDA), glutathione (GSH), and prolidase levels were kept at -20°C until they were used.Results: Serum prolidase activity and MDA levels were significantly higher in renal cancer patients than in controls (all, p < 0.05), while SOD, GSHPx, and GST levels were significantly lower (p < 0.05).Conclusion: Our results indicate that increased prolidase seems to be related to increased oxidative stress along with decreased antioxidant levels in renal cancer.
The present work aimed to evaluate the oxidative stress of nanoalumina (aluminium oxide nanoparticles, Al2O3-NPs) with a diameter <13 nm (9.83 ± 1.61 nm) as assessed by the perturbations in the enzymatic and non-enzymatic antioxidants as well as lipid peroxidation (LPO) in the brain, liver and kidney of male albino rats, after 2 days of single acute dose (3.9 or 6.4 or 8.5 g/kg) injection and a sublethal dose of 1.3 g/kg once in 2 days for a period of 28 days. According to two-way analysis of variance, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities as well as the levels of glutathione (GSH) and LPO were significantly affected by the injected doses, organs and their interactions. On the other hand, in sublethal experiments, these parameters were affected by the experimental periods, organs and their interactions. Regression analysis confirmed that the activities of SOD, CAT, GPx and GSH levels in the brain, liver and kidney were inversely proportional with the acute doses, the experimental periods, and aluminium accumulated in these tissues, whereas the levels of LPO exhibited a positive relationship. Correlation coefficient indicated that oxidative stress mainly depends on aluminium accumulated in the studied organs, followed by injected doses and the experimental periods. In comparison with the corresponding controls, the acute and sublethal doses of Al2O3-NPs caused significant inhibition of the brain, hepatic and renal SOD, CAT, GPx activities and a severe marked reduction in the concentrations of GSH that were associated with a significant elevation in the levels of malondialdehyde (an indicator of LPO). In conclusion, our data indicated that rats injected with nanoalumina suffered from the oxidative stresses that were dose and time dependent. In addition, Al2O3-NPs released into the biospheres could be potentiating a risk to the environment and causing hazard effects on living organisms, including mammals.
Fluoride is present in the ground water, World Health Organization permitted level of fluoride in the ground water is 0.5 ppm. Tooth pastes, mouth washes, tea and sea fish are the sources of fluoride. Exposure to these multiple sources results in several adverse effects in addition to the fluorosis. The present study aimed to test the effect of vitamin C and Ginkgo biloba against the behavioural deficits caused by fluoride. Rats were divided into five groups with six animals in each group (n = 6). Control group received ordinary tap water with 0.5 ppm of fluoride, the remaining groups received 100 ppm of fluoride for 30 days prior to fluoride exposure. Two groups of animals received 100 mg/kg body weight of vitamin C and G. biloba for 15 days prior to fluoride exposure. After 45 days, behavioural studies (T-Maze, passive avoidance) were conducted on the experimental animals. The results of the present study showed no behavioural deficits in the control group of animals however, the rats that received fluoride water exhibited impairment in their spatial learning and memory deficits. The deficits are not marked in the vitamin C and G. biloba groups. To conclude chronic exposure to high levels of fluoride causes severe impairment in the spatial learning and memory, these deficits can be ameliorated with the vitamin C and G. biloba.
Elaeagnus angustifolia was analyzed for determination of metals, phytoconstituents, bactericidal, fungicidal and insecticidal effects and to explore its chemical and biological potential. The root, branches, leaves, stem bark and root bark parts of E. angustifolia were found to contain iron, lead, copper, cadmium, zinc, chromium, nickel and cobalt in different concentrations. Crude extract of Elaeagnus angustifolia (Ea.Cr) was tested positive for the presence of alkaloids, flavonoids, saponins and tannins. Ea.Cr and its fractions, n-hexane (Ea.Hex), ethyl acetate (Ea.EtAc) and aqueous (Ea.Aq) showed bactericidal activity against Escherichia coli and Staphylococcus aureus, while against Pseudomonas aeruginosa only Ea.Hex and Ea.EtAc were effective. When tested for antifungal effect, Ea.Cr exhibited fungicidal action against Aspergillus fumagatus, Ea.EtAc and Ea.Aq against Aspergillus flavis and Ea.EtAc against Aspergillus niger. Ea.Hex was active against all three fungal strains. The chloroform fraction (Ea.CHCl3) was found inactive against the used microbes. Ea.Cr, Ea.Hex, Ea.CHCl3, Ea.EtAc and Ea.Aq caused mortality of Tribolium castaneum and Ephestia cautella insects observed after 24 and 48 h of treatment. These data indicate that E. angustifolia exhibits different heavy metals and compound groups. Methanolic extract of E. angustifolia and its various fractions possess antibacterial, antifungal and insecticidal activities, which elucidate medicinal application of the plant.
α-Pinene (α-pinene), a bicyclic monoterpene, is present in the oils of many species of coniferous trees, most notably the pine, and is known for its diverse biological properties such as antimicrobial, anti-inflammatory, antiproliferative and antioxidant. However, there are limited data on the cytogenetic and antioxidant effects of α-pinene in cultured human blood cells (n = 5) for the first time. The purpose of this study was to investigate the genetic, oxidative, and cytotoxic effects of α-pinene in cultured human blood cells (n = 5) for the first time. Human blood cells were treated with α-pinene (0 to 200 mg/L) for 24 and 48 h, and then cytotoxicity was detected by lactate dehydrogenase (LDH) release and (3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide) (MTT) assay, while DNA damage was also analyzed by micronucleus (MN) assay, chromosomal aberration (CA) assay and 8-oxo-2-deoxyguanosine (8-OH-dG). In addition, biochemical parameters (total antioxidant capacity (TAC) and total oxidative stress (TOS)) were examined to determine oxidative effects. The results of LDH and MTT assays showed that α-pinene (at 200 mg/L) decreased cell viability. In our in vitro test systems, it was observed that α-pinene did not cause any statistically important changes in the rates of studied genotoxicity endpoints but dose-dependent alterations were observed in TAC and TOS levels. α-Pinene treatment caused increases in TAC levels (at 25 and 50 mg/L) and decreases in TOS levels (only at 200 mg/L) on human lymphocytes. In conclusion, the findings of the present study confirm for the first time that α-pinene could be a significant source of natural antioxidant compound that may have beneficial health effects.
Nanoscale titanium dioxide (TiO2), which is massively produced and widely used in living environment, seems to have a potential risk on human health. The central nervous system (CNS) is the potential susceptible target of nanoparticles, but the studies on this aspect are limited so far. The aim of this study was to evaluate the effects of exposure to TiO2 nanoparticles during lactation period on learning and memory of offspring. Lactating Wistar rats were exposed to TiO2 nanoparticles (100 mg/kg; gavage) for 21 days. The Morris water maze and passive avoidance tests showed that the exposure to TiO2 nanoparticles could significantly impair the memory and learning in the offspring. Therefore, the application of TiO2 nanoparticles and the effects of their exposure, especially during developmental period on human brain should be cautious.
Paraquat has been shown to be a highly toxic compound for humans and animals, and many cases of acute poisoning and death have been reported over the past few decades. The present study was undertaken to evaluate comprehensively herbicides (Paraquat) and some plant extracts to biochemical aspects of Lymnaea natalensis snails. It was found that the exposure of L. natalensis to Paraquat and plant extracts led to a significant reduction in the infectivity of Fasciola gigantica miracidia to the snail. The glucose level in hemolymph of exposed snails was elevated, while the glycogen showed a decrease in soft tissues when compared with the control group. In addition, the activity level of some enzymes representing glycolytic enzymes as hexokinase (HK), pyruvate kinase (PK), phosphofructokinase (PFK), lactate dehydrogenase (LDH), and glucose phosphate isomerase (GPI) in snail’s tissues were reduced in response to the treatment. It was concluded that the pollution of the aquatic environment by herbicide would adversely affect the metabolism of the L. natalensis snails. Snails treated with Agave attenuate, Ammi visnaga, and Canna iridiflora plant had less toxic effect compared to snails treated with Paraquat.
This article reports in silico analysis of methyl isocyanate (MIC) on different key immune proteins against Mycobacterium tuberculosis. The analysis shows that MIC is released in the Bhopal gas tragedy in 1984, which is highly toxic and extremely hazardous to human health. In this study, we have selected immune proteins to perform molecular docking with the help of Autodock 4.0. Results show that the CD40 ligand and alpha5beta1 integrin have higher inhibition compared to plasminogen activator urokinase, human glutathione synthetase, mitogen-activated protein kinase (P38 MAPK 14), surfactant protein-B, -D (SP-D), and pulmonary SP-D. MIC interacted with His-125, Try-146 residue of CD40 ligand and Ala-149, and Arg-152 residue of alpha5beta1 integrin and affects the proteins functioning by binding on their active sites. These inhibitory conformations were energetically and statistically favored and supported the evidence from wet laboratory experiments reported in the literature. We can conclude that MIC directly or indirectly affects these proteins, which shows that survivals of the disaster suffer from the diseases like tuberculosis infection and lung cancer.
Environmental and occupational exposure to chromium compounds, especially hexavalent chromium (Cr(VI)), is widely recognized as potentially hepatotoxic in humans and animals. Its toxicity is associated with overproduction of free radicals, which induces oxidative damage. This study focused on the possible protective effect of propylthiouracil (PTU) against potassium dichromate (K2Cr2O7). Female mice were divided into four groups (groups I–IV) with seven animals in each group. Group I served as a control, which received tap water; group II received K2Cr2O7 alone (75 mg kg-1 body weight (b.w.)) via drinking water; group III received both K2Cr2O7 via drinking water and PTU by intramuscular injection at a dose 2.5 mg/100 g-1 b.w. twice a week, and group IV received PTU alone twice a week for 30 days. Exposure of mice to Cr promoted oxidative stress with an increase in malondialdehyde, protein carbonyl, and advanced oxidation protein product levels. Nonenzymatic antioxidants such as glutathione, nonprotein thiol, vitamin C levels and enzymatic antioxidant activities such as glutathione peroxidase and superoxide dismutase were decreased, while catalase activity was increased. Biomarkers of liver injury such as aspartate and alanine transaminases, lactate dehydrogenase activities, bilirubin, albumin, and glucose levels were increased, while triglyceride and cholesterol levels decreased. Coadministration of PTU restored the above-mentioned parameters to near-normal values. The histological findings confirmed the biochemical results.
n-Heneicosane (C21) is one of the vital pheromone for attracting mosquitoes of Aedes spp to lay their eggs in areas of stagnant fresh water, for their subsequent destruction, thus controlling spread of dangerous disease transmission by the vectors. As part of a safety evaluation, we have investigated embryo toxic and teratogenic potential, if any, of C21 following OECD Test Guideline 414. C21 was offered at a dose of 1 g/kg body weight mixed in the standard rat pellet diet to treated rats, whereas the control group received only standard rat pellet diet. There were no mortalities and animals did not show any clinical signs of toxicity. A similar pattern of body weight gain, feed and water intake was observed in treated and control groups. Analysis of maternal toxic response, maternal end points of development of the foetus and developmental end points for litters did not show any gross structural abnormality in dams or foetus of treated group compared to that of the control group. Thus, it was concluded that C21 at a dose of 1 g/kg was neither embryo toxic nor teratogenic in Wister rats. Furthermore, the no observed adverse effect level for teratogenicity for C21 in rats may be considered as 1 g/kg body weight under the present experimental conditions.
Feasible regeneration protocol for economically important plant Eruca sativa was established and 1, 1-diphenyl-2-picrylhydrazyl scavenging activity of regenerated tissues was evaluated and compared with plant material collected from the wild. Leaf portions inoculated onto Murashige and Skoog (MS) medium responded to all plant growth regulators exploited. Optimum callus production was achieved on a combination of 2.0 mg l-1 6-benzyladenine (BA) + 1.0 mg l-1 α-naphthalene acetic acid (NAA) and the lowest response was recorded for 0.5 mg l-1 gibberellic acid (GA3) + 1.0 mg l-1 NAA. The callus was subcultured on similar composition/concentrations of plant growth regulators after 4 weeks of culture time. A 5.0 mg l-1 6-BA + 1.0 mg l-1 NAA produced optimum percentage shoot organogenesis after 4 weeks of subculturing. However, optimum number of shoots per explant was recorded for moderate concentrations (1.0 and 2.0 mg l-1) of kinetin. Incorporation of NAA into MS medium-containing GA3 also produced a feasible number of shoots/explant. Similar mean shoot length was recorded for 2.0 mg l-1 kinetin + 1.0 mg l-1 NAA and optimum concentrations (2.0, 5.0, and 10.0 mg l-1) of GA3 + 1.0 mg l-1 NAA. In vitro generated shoots were shifted to MS medium augmented with indole acetic acid (IAA) for rooting after 4 weeks of subculturing. Moderate concentrations (5.0 mg l-1) of IAA produced feasible rooting. Investigation of radical scavenging activity showed that callus possesses higher levels of radical scavengers than other plant tissues tested. Phenolics and glucosides are reported to be active components of Eruca sativa phytochemistry.
The herbicide itself and the degradation products are highly toxic on biological systems. The aim of this study is to investigate the potential toxic effects of trifluralin (TRF) on the urinary system of male rats and to investigate the protective effects of resveratrol (RSV) in TRF-induced urinary system damage. A total of 35 male Wistar rats were randomly divided into: (1) control group, (2) sham group, (3) low dose TRF group (0.8 g/kg/day), (4) high dose TRF group (2 g/kg/day) and (5) high dose TRF + RSV group 10 mg/kg/day. RSV was administered for 21 days by intragastric gavage at a dose of 10 mg/kg/day after induction of TRF. Kidney, ureter and urinary bladder tissue was examined using light microscopy and ultrastructurally. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling was performed to detect apoptosis. Superoxide dismutase (SOD), glutathion peroxidase (GPx) and malondialdehyde (MDA) levels were also evaluated biochemically for oxidative stress parameters. Histological evaluation showed that TRF increases apoptosis and oxidative stress, causes histological tissue damages and biochemical changes in the kidneys but does not cause any damage to the ureter and bladder. Treatment with RSV significantly attenuated tissue damage in the urinary system of rats. Apopitotic cells were significantly decreased in the treatment group. Additionally, treatment with RSV decreased SOD and GPx levels and increased MDA levels in the kidney tissue of animals subjected to TRF. These results show that RSV can significantly minimize histological damage and biochemical differences in treating TRF-induced kidney injury in rats.
The hypothesis that two known chelators deferasirox (4-[3,5-bis(2-hydroxyphenyl)-1,2,4-triazol-1-yl]-benzoic acid) and desferrioxamine (DFO) might be more efficient as combined treatment than as monotherapies in removing thallium from the body was tested in a new acute rat model. 7-week-old male Wistar rats received chelators: deferasirox (orally), DFO (intraperitoneal; i.p.), or deferasirox + DFO as 75 or 150 mg/kg dose half an hour after a single i.p. administration of 8 mg thallium/kg body weight in the form of chloride. Serum thallium concentration, urinary thallium, and iron excretions were determined by graphite furnace atomic absorption spectrometry. Both chelators were effective only at the higher dose level, while DFO was more effective than deferasirox in enhancing urinary thallium excretion, deferasirox was more effective than DFO in enhancing urinary iron excretion. In the combined treatment group, deferasirox did not increase the DFO effect on thallium and DFO did not increase the effect of deferasirox on iron elimination. Our results support the usefulness of this animal model for preliminary in vivo testing of thallium chelators. Urinary values were more useful because of the high variability of serum results.
High fructose consumption is currently linked to metabolic disorders including insulin resistance and dyslipidemia as well as hepatic steatosis. Dimethyl dimethoxy biphenyl dicarboxylate (DDB) is a hepatoprotectant with antioxidant and anti-inflammatory properties. The aim of this study therefore is to evaluate the effect of DDB on high fructose-induced metabolic disturbances and hepatic steatosis in a rat model. Male Wistar rats were allocated into three groups: control, fructose-fed (10% in drinking water and 10% in diet), and fructose-fed DDB (300 mg/kg, orally)-treated groups. Rats were fed a high-fructose diet for 6 weeks, while DDB was administered for an additional 2 weeks. High-fructose consumption elevated serum glucose and insulin levels and impaired oral glucose tolerance test, revealing insulin resistance. It also increased serum triglycerides and alanine aminotransferase as well as visceral fat content and decreased serum high-density lipoprotein. Additionally, histopathological examination revealed that high fructose intake induced hepatic steatosis. These alterations were associated with increased serum uric acid as well as hepatic content of malondialdehyde and nitric oxide (NO) in addition to overexpression of inducible NO synthase (iNOS). DDB administration significantly ameliorated the high fructose-induced hepatic and metabolic alterations. In conclusion, DDB ameliorates high fructose-induced metabolic disorders and hepatic steatosis in rats. Such protection is, at least in part, due to the inhibition of lipid peroxidation, decrease in iNOS overexpression, and reduction of elevated uric acid.
Natural products possessing antioxidant properties play a very crucial role in ameliorating deleterious effects of reactive oxygen species. This study investigated the chemoprotective properties of methanolic extract of Vernonia amygdalina (MEVA) in an experimental model of hepatic oxidative damage induced by 2-acetylaminofluorene (2-AAF). Rats were divided into six groups. Groups 1 and 2 received saline and dimethyl sulfoxide, respectively, and served as controls. Group 3 received MEVA at a dose of 250 mg/kg, while groups 5 and 6 were pretreated for 14 days with MEVA at 250 mg/kg and 500 mg/kg doses before coadministration with 2-AAF at 100 mg/kg for another 7 days. 2-AAF was administered to group 4 for the last 7 days. Animals were killed 24 h after the last administration of 2-AAF. 2-AAF significantly (p < 0.05) induced marked hepatic damage as revealed by increased activities of serum enzymes such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and -glutamyl transferase and bilirubin concentration. 2-AAF also elicited decrease in the activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione-S-transferase, and glutathione peroxidase, depletion of reduced glutathione, and increase in malondialdehyde levels. The activities of glucose-6-phosphatase and 5'-nucleotidase were also depleted. MEVA at 250 mg/kg and 500 mg/kg significantly (p < 0.05) ameliorated the oxidative damage, functional impairments, and histopathological changes associated with 2-AAF toxicity by reducing the activities of serum enzymes, upregulating the antioxidant defense enzymes and glutathione with decrease in malondialdehyde level. In this study, the revealed ameliorative and hepatoprotective effects of MEVA against 2-AAF-induced toxicity may be due to its antioxidant and free-radical scavenging activities, thus suggesting its usefulness as a possible chemoprophylactic agent.
Metastasis-associated protein 1 (MTA1) is involved in tumor growth and metastasis of cancers. Being a component of nucleosome remodeling and histone deacetylase complex, the protein is also associated with DNA damage response pathway. Since the protein is involved in cancer pathology, we first investigated the effects of bleomycin, etoposide, and cisplatin (BEP) on MTA1 signaling in the testis. Second, since the antioxidants (AOs) have protective effects, we further investigated whether or not an AO cocktail modulates the effects of the drugs. Adult male Sprague Dawley rats (N = 4) were treated either with saline, or AO (α-tocopherol, <sc>l</sc>-ascorbic acid, zinc, and selenium), or therapeutic dose levels of etoposide (15 mg/kg) and cisplatin (3 mg/kg) from day 1–4 of the week and B (1.5 mg/kg) on the second day of the week, or BEP + AO. The real-time polymerase chain reaction showed that MTA1 and MTA1s (short form) gene expression was downregulated in AO (100% and 100%), BEP (86% and 71%), and BEP + AO (97% and 93%) groups. Western blotting and immunohistochemistry results showed that unnormalized MTA1 protein expression was upregulated in AO (38%) and BEP + AO (34%) groups; however, the MTA1/β-actin ratio was upregulated in all treated groups (21, 19, and 15%, respectively). In conclusion, the results indicate that both BEP and AO suppress MTA1 and MTA1s transcription, which may render the germ cells to be more prone to apoptosis. However, upregulation of MTA1 protein expression may be related to induced DNA damage. Modulation of MTA1 signaling is a novel mechanism of action of BEP and AO, which may be useful in developing newer anticancer drugs.
Amiodarone is a potent antiarrhythmic drug that is used to treat ventricular and supraventricular tachyarrhythmias. The present work studied the effect of amiodarone on the kidney of albino rats and the possible ameliorative role of grapefruit juice. Administration of amiodarone by gastric intubation (18 mg/kg body weight (b.w.), daily for 5 weeks) caused many histological alterations including intertubular leucocytic infiltrations, degeneration of the renal tubules, and atrophy of the glomeruli. Amiodarone caused marked elevation in serum creatinine and blood urea nitrogen. Histochemical examination of the renal tubules revealed depletion of glycogen and total proteins. Besides, animals administered with amiodarone showed an increase of apoptotic bands as detected by gel electrophoresis. Treating animals with amiodarone and grapefruit juice (27 ml/kg b.w.) caused an improvement in histological and histochemical appearance of the kidney together with decrease of serum creatinine and blood urea nitrogen. Moreover, the apoptosis was decreased. It is concluded from the obtained results that grapefruit juice ameliorates the nephrotoxicity of amiodarone in albino rats and this may be due to the potent antioxidant effects of its components.
The use of electrical devices has gradually increased throughout the last century, and scientists have suggested that electromagnetic fields (EMF) generated by such devices may have harmful effects on living creatures. This work represents a systematic review of collective scholarly literature examining the effects of EMFs on the heart. Although most works describing effects of EMF exposure have been carried out using city electric frequencies (50–60 Hz), a consensus has not been reached about whether long- or short-term exposure to 50–60 Hz EMF negatively affects the heart. Studies have indicated that EMFs produced at cell-phone frequencies cause no-effect on the heart. Differences between results of studies may be due to a compensatory response developed by the body over time. At greater EMF strengths or shorter exposures, the ability of the body to develop compensation mechanisms is reduced and the potential for heart-related effects increases. It is noteworthy that diseases of heart tissues such as myocardial ischemia can also be successfully treated using EMF. Despite the substantial volume of data that has been collected on heart-related effects of EMFs, additional studies are needed at the cellular and molecular level to fully clarify the subject. Until the effects of EMF on heart tissue are more fully explored, electronic devices generating EMFs should be approached with caution.
Acetaminophen (APAP) is widely used in the treatment of pain. Toxic doses of APAP cause acute liver failure, but therapeutic doses are believed to be safe. The purpose of this study is to investigate the effects of administration of subtoxic doses of APAP on liver and blood levels of insulin-like growth factor-1 (IGF-1) in rats. Low dose (100 mg/kg) and high dose (250 mg/kg) of APAP were intraperitoneally injected into Wistar albino rats. Following administration of therapeutic doses of APAP, there were no significant changes in serum transaminases and liver glutathione levels. Both doses of APAP induced a decrease in liver and blood levels of IGF-1 when compared with the controls. There was no significant difference in liver IGF-1 levels between the high-dose and low-dose APAP groups; however, there was a significant difference in blood IGF-1 levels between both the groups. The histological examination showed that low dose of APAP induced mild degree of structural change, while high dose of APAP induced severe structural damage. In conclusion, these results suggest that blood IGF-1 levels may have a value in predicting hepatic damage resulting from therapeutic doses of APAP.
Cyclosporin A (CsA) is the most widely used immunosuppressive drug for preventing graft rejection and autoimmune disease. However, the therapeutic treatment induces several side effects such as nephrotoxicity, cardiotoxicity, hypertension, and hepatotoxicity. Curcumin has been successfully used as a potent antioxidant against many pathophysiological states. This experimental study was performed to test, during CsA treatment, the alterations of curcumin antioxidant properties against CsA-induced endothelial dysfunction. Rats were divided into four groups: control, curcumin alone, CsA, and CsA + curcumin; each group containing eight animals. The animals in the CsA + curcumin group were treated with CsA (10 days, 25 mg/kg, orally) and curcumin (15 days, 200 mg/kg, orally, starting 5 days before CsA administration). At the end of the treatments, the animals were killed; serum and aorta tissue were treated for biochemical and morphological analyses. The results indicate that CsA-induced aortic endothelial dysfunction was characterized by morphological and ultrastructural alterations in tissue architecture, changes in malondialdehyde and ferric reducing/antioxidant power levels, and increase in endothelial nitric oxide synthase and terminal-deoxynucleotidyl-transferase mediated dUTP nick end labeling (TUNEL) expression. In conclusion, our data suggest that the imbalance between production of free oxygen radicals and antioxidant defence systems, due to CsA administration, is a mechanism responsible for oxidative stress. Moreover, we show that curcumin plays a protective action against CsA-induced endothelial dysfunction and oxidative stress, as supported by biochemical, ultrastructural, immunohistochemical, and TUNEL results.
Ascorbic acid (AA) is a naturally occurring phenolic compound with antioxidant properties used in food, cosmetics, and pharmaceutical products. In this study, the effect of AA on ferric nitrilotriacetate (Fe-NTA)-induced hepatotoxicity in rats has been examined. Fe-NTA alone enhances ornithine decarboxylase activity to 4.5-fold and tritiated thymidine incorporation in DNA to 3.6-fold in livers compared with the corresponding saline-treated controls. The enhanced ornithine decarboxylase activity and DNA synthesis showed a reduction to 3.02- and 1.88-fold, respectively, at a higher dose of 2 mg AA per day per animal, compared with the Fe-NTA-treated groups. Fe-NTA treatment also enhanced the hepatic microsomal lipid peroxidation to 1.7-fold compared to saline-treated controls. These changes were reversed significantly in animals receiving pretreatment of AA. The present data shows that AA can reciprocate the toxic effects of Fe-NTA and can serve as a potent chemopreventive agent to suppress oxidant-induced tissue injury and hepatotoxicity in rats.
This study evaluates the influence of estrogen hormone on the experimentally induced asthma in male mice. The animals were divided into four groups, with 20 mice in each group; group I (control mice) included mice that received no treatment, group II included mice that received intraperitoneal estrogen injection (0.25 mg/kg body weight (bw), twice on day 28 of the experiment), group III (asthmatic mice) included asthmatic mice that received intraperitoneal injection of two doses of ovalbumin (OVA; 2 µg of OVA mixed with 100 µg of aluminum potassium sulfate) on days 1 and 14 of the experiment and then challenged intranasally with a single dose of OVA (50 µg dissolved in 0.05 ml phosphate-buffered saline; PBS) on day 28 of the experiment, and group IV (asthmatic mice treated with estrogen) included asthma model male mice that received the estrogen (0.5 mg/kg bw in 40 ml PBS, twice on the day 28 of the experiment). The immunohistochemical studies observed a marked intensity of CD15 immunoreactivity in the lung tissues of asthma model mice. Physiological results recorded that the total and differential count of leukocytes in bronchoalveolar lavage fluid (BALF) of asthma model mice recorded a significant increase in the number of leukocytes especially in the number of eosinophil cells. The BALF of asthma model mice showed high levels of interleukins 4 and 5 (IL-4 and IL-5), and there was a significant decrease in both the levels of IL-4 and IL-5 in BALF of asthma model mice treated with estrogen. In conclusion, the obtained results indicated that the asthma is responsible for certain immunohistochemical and physiological alterations induced in lung tissues of mice. The administration of estrogen to asthmatic male mice could improve these changes. For this reason, the present findings support the possible role of estrogen in modulating the inflammatory effects caused by asthma in male mice and may be helpful to cure many asthmatic progressions.
Environmental pollution of water, which is a source of cheap and affordable protein in the form of fish on which the population depends on, is of great concern globally. The present study assesses the levels of polychlorinated biphenyls (PCBs) congeners in sediments and six commonly consumed cichlid species from Eleyele Reservoir, Southwestern Nigeria. The results indicate that the concentrations of heavier PCB congeners are higher than the lighter congeners in both sediment and fish tissue. The predominant PCB congeners in the sediment samples from this site were PCBs 8, 44, 114, 101, 189, 196, 206 and 209. The concentration of PCB congeners increased with increasing molecular weight from hepta-PCB to deca-PCB in all fish species. The trend in accumulation of total PCBs in fish was as follows: Tilapia guineensis (2,531.1 ± 74.6 ng/g) > Sarotherodon galilaeus (1178.7 ± 68.5 ng/g) > Oreochromis niloticus > (891.8 ± 49.6 ng/g) > Tilapia zillii (832.8 ± 38.2 ng/g) > Hemichromis fasciatus (475.7 ± 28.5 ng/g) > Sarotherodon melanotheron (333.2 ± 26.1 ng/g). In summary, data from this study shows that the levels of PCBs in cichlid species from Eleyele Reservoir are higher than the threshold level of 0.023–0.047 ng g-1 recommended by United States Environmental Protection Agency. Such elevated PCB levels present significant health implications for human consumers and a threat to the resident fish communities.
Caffeic acid phenethyl ester (CAPE) has antioxidant and anti-inflammatory properties. The aim of this study is to examine the negative effects of toluene on kidney tissues and functions and to investigate the protective effects of CAPE against toluene-induced nephrotoxicity in rats. A total of 21 male Wistar rats were divided into three groups of equal number in each. The rats in group I were the controls. Toluene was intraperitoneally injected into the rats in group II with a dose of 500 mg/kg. Rats in group III received CAPE daily while exposed to toluene. After 14 days of experimental period, all rats were killed by decapitation. Enzymatic activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) and malondialdehyde (MDA) levels were studied in the rat kidneys. Blood urea nitrogen (BUN) and serum creatinine levels were measured for renal function. The CAT and SOD enzyme activities and serum creatinine levels were significantly increased in rats treated with toluene when compared with the controls. But GSH-Px activity, MDA, and BUN levels showed statistically nonsignificant changes. However, increased CAT and SOD enzyme activities and decreased serum creatinine levels were detected in the rats that received CAPE while exposed to toluene. The GSH-Px activity and MDA and BUN levels in the same group did not show statistically significant changes. The results of our study demonstrated that toluene damages kidney tissue and is a nephrotoxic substance. CAPE was able to prevent the renal damage as antioxidant, antitoxic, and nephroprotective agent.
Lifeguards are frequently exposed to various irritant chemicals including chlorine during work, which can induce respiratory and allergic disorders. In this study, pulmonary function tests (PFTs) and self-reported respiratory and allergic symptoms in lifeguards were compared with matched control subjects. The frequency of respiratory and allergic symptoms was evaluated in a sample of 38 Iranian male lifeguards and 38 control subjects with similar age, having other jobs from the general population, using a questionnaire including questions on work-related respiratory and allergic symptoms in the past year, smoking habits, and duration of working as a lifeguard. PFTs were also measured in lifeguard subjects before and 15 min after 200 µg inhaled salbutamol and baseline PFT in controls. A total of 22 (55%) participants reported work-related respiratory symptoms. Sputum (39.4%) and cough (18.4%) were the most common symptoms and only 7.9% and 15.8% of lifeguards reported wheezing and shortness of breath, respectively. Both sputum and breathlessness were significantly higher in lifeguards than control group (p < 0.05 and p < 0.005, respectively). Most allergic symptoms (sneezing and runny nose) in lifeguards were also significantly greater than control group (p < 0.05 for both cases). In addition, all respiratory (except sputum and wheezing) and allergic symptoms were significantly higher in lifeguards during work compared with rest period (p < 0.05 to p < 0.005). Most PFT values were also significantly lower in lifeguards than control subjects (p < 0.05 to p < 0.001). In addition, most (all) PFT values were significantly improved after 200 µg inhaled salbutamol (p < 0.05 to p < 0.001). These results showed that lifeguards have higher frequencies of work related respiratory symptoms and allergic symptoms particularly during the work period. PFT values were also significantly reduced among lifeguards.
Toxicity and accumulation of cadmium in body organs by eating contaminated food has an important role in endangering a human's health. Using Environmental Protection Agency (EPA) reports, site 1, site 2 and site 3 were selected as polluted sites and site 4 was selected as the control site. Seedlings of buttonwood were prepared for 12 months then root, stem, and leaf samples were harvested and the amounts of cadmium element in stem and leaf organs together with the growth parameters were measured. This study determines the amount of cadmium accumulated in Platanus occidentalis. The respective cadmium concentrations in the root, leaf, and stem in site 1 were 382, 98, and 87; in site 2 they were 591, 122, and 94; and in site 3 they were 633, 151, and 104 mg/kg dry weight (DW). Furthermore, the comparison between accumulation and transfer of cadmium in the study showed more absorption of this metal by the root than that by the stem and leaf. The result of this research shows that buttonwood has the potential for cadmium accumulation without any serious damage to its growth. To control the extent of contamination in industrial areas, petrochemical industries, power plants and vast contaminated municipal areas, there is a great need for planting plants like buttonwood.
The study explored variations in the life cycle parameters in Drosophila melanogaster as a function of treatment with fluorinated insecticide, cryolite. Some of the life cycle parameters considered in this study were larval duration, pupal duration, and percentage of adult fly emergence in D. melanogaster of Oregon R strain. Freshly hatched first instar larvae were transferred to different dietary concentrations of the test chemical (5, 10, 15, 20, 40, 60, 80, 100, 150, and 200 ppm). Larval duration, pupal duration, and the emergence of flies of both treated and control groups were recorded. Results obtained show a significant (p < 0.001–0.05) change in the mentioned parameters in the treated flies when compared with the controls. Interestingly, the percentage emergence of flies shows a decreasing trend along with increase in treatment concentration and almost no detectable emergence is observed in 200 ppm treatment category until the 20th day of experiment. Thus, the study indicates insecticide-induced variation in duration of different life stages and thereby suggests an effect of the fluorinated insecticide on the biology of a nontarget organism like Drosophila.
Carbofuran (2,3-dihydro-2,2-dimethyl-7-benzofuranyl methylcarbamate; C12H15NO3) is one of the most toxic carbamate pesticides. For acute toxicity of carbofuran, juveniles of Macrobrachium olfersii were exposed to different concentrations of carbofuran using the static renewal method at different temperature levels (15, 20 and 25°C) at pH 7.0. The main purpose of the present study was to detect the acute toxicity of carbofuran to M. olfersii and investigate its effects on oxygen consumption and ammonium excretion; these tests have not been carried out in this species before. First, the acute toxicity – median lethal concentration – of carbofuran to M. olfersii for 24, 48, 72 and 96 h was examined, which resulted in the following values: 1.64, 1.22, 0.86 and 0.42 mg L-1, respectively. Furthermore, we also found that carbofuran caused an inhibition in oxygen consumption of 60.6, 65.3 and 66.2% with respect to the control. In addition, after separate exposures to carbofuran, elevations in ammonium excretion were more than 500% with respect to the control.
The present study is an unsubstantiated qualitative assessment of the abused drugs—tramadol and clonazepam. The aim of this study is to evaluate whether the effects of tramadol, clonazepam, and their combination on mitochondrial electron transport chain (ETC) complexes were influential at therapeutic or at progressively increasing doses. The study comprised of a total of 70 healthy male rats, aged 3 months. According to the drug intake regimen, animals were divided into seven groups: control, tramadol therapeutic, clonazepam therapeutic, combination therapeutic, tramadol abuse, clonazepam abuse, and combination abuse group. At the end of the experiment, brain mitochondrial ETC complexes (I, II, III, and IV) were evaluated. Histopathological examinations were also performed on brain tissues. The results showed that groups that received tramadol (therapeutic and abuse) suffered from weight loss. Tramadol abuse group and combination abuse group showed significant decrease in the activities of I, III, and IV complexes but not in the activity of complex II. In conclusion, tramadol but not clonazepam has been found to partially inhibit the activities of respiratory chain complexes I, III, and IV but not the activity of complex II and such inhibition occurred only at doses that exceeded the maximum recommended adult human daily therapeutic doses. This result explains the clinical and histopathological effects of tramadol, such as seizures and red neurons (marker for apoptosis), respectively.
The purpose of this study was to assess the preventive effects of -carnitine (LC) against DNA damage induced by diazinon (DZN) in rat blood lymphocytes. Animals were concurrently administered intraperitoneally with DZN in proper solvent (20 mg/kg body weight (b.w.)) and LC at three different doses (50, 100, and 150 mg/kg b.w.) for 30 consecutive days. The positive control group received DZN at the same dose without LC. 24 hours after last injection, 0.5 ml blood of each rat was received and cultured in culture medium for 44 h. The lymphocyte cultures were mitogenically stimulated with cytochalasin B for the evaluation of the number of micronuclei (MNs) in cytokinesis-blocked binucleated cells. Incubation of lymphocytes with DZN induced additional genotoxicity and was shown by increase in MNs frequency in rat lymphocytes. LC at all doses had a protective effect and significantly reduced the MNs frequency in cultured lymphocytes (p < 0.0001–p < 0.05). The maximum effect was observed at 150 mg/kg that reduced the frequency of MN from 12.78 ± 0.24% for DZN group to 5.61 ± 0.17%. Our study revealed that LC has a potent antigenotoxic effect against DZN-induced toxicity in rats, which may be due to the scavenging of free radicals and increased antioxidant status. Since LC is a natural compound and safe, it is recommended as a daily supplement for defense against side-effects induced by chemical hazardous agents.
Phthalate compounds are widely used industrial chemicals; when incorporated into polyvinyl chloride, they are not covalently bound and released into the surrounding media. Some of them have estrogenic potential in vitro but data on in vivo studies are scanty. For the 3-day uterotrophic assay, di-n-butyl phthalate (DBP;10 and 100 mg/kg), butyl benzyl phthalate (BBP; 20 and 200 mg/kg), and diethylstilbestrol (DES, 40 µg/kg, positive control) were administered orally to immature female rats for three consecutive days from postnatal day (PND) 21. For the 20-day pubertal onset assay, DBP (10 and 20 mg/kg), BBP (20 and 200 mg/kg), and DES (6 µg/kg) were administered orally from PND 21 daily for 20 days. In the uterotrophic assay, in groups treated with higher dose of DBP and BBP, the uterine wet weight significantly decreased in the higher dose, and there were minor variations in the ovary wet weight, while the wet weight of these organs increased significantly in DES-treated group. In the 20-day pubertal assay, the weight of uterus and ovary declined significantly and changes in vaginal weight were nonsignificant in DBP- and BBP-treated groups. However, in DES-treated group nonsignificant elevation in vagina weight was observed. All the DES-treated animals showed the vaginal opening (VO) on day 26.17 ± 0.16. However, VO was not observed in any of the animals in control, vehicle control, BBP-, and DBP-treated groups up to PND 42, except in one animal each in vehicle control and DBP (100 mg/kg)-treated groups. The data indicated that both DBP and BBP were unable to induce elevation in the uterine and ovarian weight. While DES treatment can accelerate the growth of uterus and ovary and alter the onset of puberty and estrous cyclicity in prepubertal rats. These suggest that these compounds may not have estrogenic potential in vivo.
The present study was undertaken to estimate the effect of occupational exposure to lead on the blood concentration of glucose and several enzymes involved in glycolysis, the citric acid cycle, and the pentose phosphate pathway. To estimate the degree of lipid peroxidation, the concentrations of conjugated dienes were determined.
The examined group included 145 healthy male employees of lead–zinc works. Taking into account the mean blood lead levels, the examined group was divided into two subgroups. The control group was composed of 36 healthy male administrative workers.
The markers of lead exposure were significantly elevated in both subgroups when compared with the controls. There were no significant changes in fasting glucose concentration and fructose-1,6-bisphosphate aldolase activity in the study population. The concentration of conjugated dienes was significantly higher in both subgroups, whereas the activity of malate dehydrogenase was significantly higher only in the group with higher exposure. The activities of lactate dehydrogenase and sorbitol dehydrogenase were significantly decreased in the examined subgroups. The activity of glucose-6-phosphate dehydrogenase decreased significantly in the group with higher exposure and could be the cause of the elevated concentrations of conjugated dienes.
It is possible to conclude that lead interferes with carbohydrate metabolism, but compensatory mechanisms seem to be efficient, as glucose homeostasis in lead-exposed workers was not disturbed.
Lichens are symbiotic organisms composed of a fungus joined to a photosynthesizing partner that can be either an alga or a cyanobacterium. They can be used as a novel bioresource for natural antioxidants. However, there is also a need for further studies to validate the lichens used in medicinal remedies. This study covers the previously unrecognized effects of Cetraria islandica (CIAE) and Pseudevernia furfuracea (PFAE) in streptozotocin (STZ)-induced diabetes. In experimental design, control or diabetic rats were either untreated or treated with aqueous lichen extracts (250–500 mg/kg/day) for 2 weeks starting at 72 h after STZ injection. On day 14, animals were anesthetized, metabolic and biochemical parameters were appreciated between control and treatment groups. The histopathology of kidney was examined using four different staining methods: hematoxylin–eosin (H&E), periodic acid-Schiff (PAS), Masson trichrome and Congo red. Our experimental data showed that increasing doses of CIAE and PFAE did not have any detrimental effects on the studied parameters and the malondialdehyde level of kidney. CIAE extract showed prominent results compared to doses of PFAE extract for antioxidant capacity. However, the protective effect of CIAE extract was inadequate on diabetes-induced disorders and kidney damages. Moreover, animals subjected to diabetes mellitus (DM) therapy unfortunately did not benefit from the usage of increasing lichen doses due to their unchanged antioxidant activity to tissue. The results obtained in the present study suggest that CIAE and PFAE are safe but their power is limited because of the intensive oxidative stress in kidney of type 1 diabetic rats. It is also implied that CIAE extract is especially suitable for different administration routes in DM.
Lead (Pb), as other environmental neurotoxicant substances, has the capability to interfere with many biochemical events present in cells throughout the body. In the present study, the environmental and occupational exposure to Pb has been assessed by analyzing the scalp hair samples of male adolescents aged 12–15 years, who have worked for the last 12–36 months in Pb battery recycling workshops (BRWs). For comparative purposes, gender and age-matched subjects living in the vicinity of recycling workshops as well as in areas without industrial activity were used as controls. The scalp hair samples were oxidized by acid in a microwave oven prior to determination of Pb by electrothermal atomic absorption spectrometry. The results indicated that both workers and nonworking exposed subjects had higher levels of Pb than nonexposed controls. The contents of Pb in scalp hair of adolescent workers in the present study were compared with those reported in other studies.
Aflatoxin B1 (AFB1) is a toxic compound commonly found as a contaminant in human food. It is carcinogenic due its potential in inducing the oxidative stress and distortion of the most antioxidant enzymes. Since black tea possesses strong antioxidant activity, it protects cells and tissues against oxidative stress. Curcumin (CMN), a naturally occurring agent, has a combination of biological and pharmacological properties that include antioxidant activity. Therefore, the present study was carried out to investigate the possible role of separate and mixed supplementation of black tea extract and CMN in the hepatotoxicity induced by AFB1 in rats. A total of 48 adult male Sprague Dawley rats were randomly divided into eight groups with six rats in each group. Group 1 (normal control) includes rats that received no treatment. Groups 2, 3, and 4 (positive control) include rats that received olive oil, black tea extract, and CMN, respectively. Group 5 includes rats that received AFB1 at a dose of 750 μg/kg body weight (b.w.) dissolved in olive oil. Groups 6, 7, and 8 include rats that received AFB1 along with 2% black tea extract, CMN at a dose of 200 mg/kg b.w., and both black tea extract and CMN at the same previous doses, respectively. After 90 days, biochemical and histopathological examination was carried out for the blood samples and liver tissues. A significant decrease in the antioxidant enzymes and a significant increase in the lipid peroxidation and hydrogen peroxide in the rats treated with AFB1 were observed. Moreover, there were dramatic changes in the liver function biomarkers, lipid profile, and liver architecture. Supplementation of black tea extract or CMN showed an efficient role in repairing the distortion of the biochemical and histological changes induced by AFB1 in liver. This improvement was more pronounced when both CMN and black tea were used together.
This research work was planned to investigate the antioxidant potential of methanolic crude extract of Oxalis corniculata (OCME) against lung injuries initiated by carbon tetrachloride (CCl4) in rats at histological and biochemical level. A total of 42 female Sprague Dawley rats were randomly distributed in to seven groups and each group comprised of six rats. Experiment was completed in 22 days (10 doses at alternate days). Group I was not treated (control rats), while group II was administered with vehicles (olive oil and dimethyl sulfoxide), groups III, IV, and V were treated with 1 ml kg-1 body weight (b.w.) of CCl4 (20% in olive oil). Group III received only CCl4, whereas groups IV and V were administered with 100 and 200 mg kg-1 b.w. of OCME, respectively. Group VI was administered with OCME (200 mg kg-1 b.w.) alone. Group VII was treated with sylimarin (50 mg kg-1 b.w.). CCl4 enhanced the lipid peroxidation while reduced the glutathione in lung samples. Activities of antioxidant enzymes, catalase, peroxidase, superoxide dismutase, and glutathione-S-transferase decreased in lung homogenates with CCl4. Treatment of CCl4 induced deleterious changes in the microanatomy of lungs by rupturing the alveolar septa, thickening of alveolar walls, and damaging the cells with subsequent collapse of blood vessels due to the accumulation of degenerated blood cells. OCME, dose dependently, prevented the alterations in these parameters. These results suggest that OCME protected the lungs due to its intrinsic properties by scavenging of free radicals generated by CCl4.
Cadmium (Cd) is one of the most dangerous occupational and environmental toxins. The objective of the present study is to examine the potential prophylactic effects of phytic acid (PA) on thyroid hormones of male rats intoxicated with Cd. The male albino rats were divided into five groups: group I (control) was fed with the basal diet, group II was intoxicated with Cd in drinking water, groups III, IV, and V were intoxicated with Cd in drinking water and fed with the diet containing 3.5, 7, and 10 g of PA/kg, respectively. The results indicated that the serum calcium, iron (Fe), and total Fe binding capacity levels and serum T3 and T4 in Cd-treated rats of group II were decreased when compared with the control group, while PA-administered groups with Cd showed a significant improvement when compared with the Cd-treated rats only. Serum thyroid stimulating hormone (TSH) level was significantly increased in Cd-treated rats compared with the control group, while the addition of PA in diet decreased the high levels of TSH. These results indicated a prophylactic effect of PA against Cd-induced toxicity in rats.
The present study examined the effects of licorice on antioxidant defense, functional impairment, histopathology, and ultrastructural alterations in isoproterenol (ISP)-induced myocardial injury in rats. Myocardial necrosis was induced by two subcutaneous injection of ISP (85 mg/kg) at an interval of 24 h. Licorice was administered orally for 30 days in the doses of 100, 200, 400, or 800 mg/kg. ISP-treated rats showed impaired hemodynamics, left ventricular dysfunction, and caused depletion of antioxidants and marker enzymes along with lipid peroxidation from myocardium. ISP also induced histopathological and ultrastructural alterations in myocardium. Pretreatment with licorice prevented the depletion of endogenous antioxidants and myocyte injury marker enzymes, inhibited lipid peroxidation, and showed recovery of hemodynamic and ventricular functions. Licorice treatment also reduced myonecrosis, edema, and infiltration of inflammatory cells and showed preservation of subcellular and ultrastructural components. Our results demonstrate that licorice exerts cardioprotection by reducing oxidative stress, augmenting endogenous antioxidants, and restoring functional parameters as well as maintaining structural integrity.
Ethnopharmacological relevance:Dalbergia sissoo Roxb. ex DC. (family: Fabaceae; Indian Rosewood), is used in India, especially in rural communities by traditional medicine practitioners to treat diarrhoea. However, scientific evidence does not exist in any literature to substantiate the claim of therapeutic success of the plant species in diarrhoea. Aim:To study the protective effect of ethanol extract from D. sissoo Roxb. ex DC. leaves (EDSL) against experimentally induced diarrhoea and peristalsis in mice. Materials and Methods:Castor oil-induced diarrhoea and magnesium sulphate (MgSO4)-induced diarrhoea tests were used to assess the antidiarrhoeal activity of D. sissoo. Gastrointestinal tract transit of charcoal meal test and barium sulphate milk was used to assess the peristalsis activity of the extract, while the acute toxicity study and determination of total phenolics and total flavonoids were carried out using well-established protocols and methods. Results:The EDSL significantly reduced faecal output in castor oil-induced and MgSO4-induced diarrhoea and also significantly reduced the number of diarrhoeal episodes. D. sissoo significantly delayed the onset of diarrhoea induced by both castor oil and MgSO4 and comparable to loperamide, a standard antidiarrhoeal drug. Both D. sissoo and atropine sulphate significantly reduced the peristalsis activity of charcoal meal and barium sulphate milk in mice. The preliminary phytochemical analysis of EDSL revealed the presence of carbohydrates, phenolics, glycosides, and flavonoids. The median lethal dose of EDSL was greater than 2000 mg/kg (orally (p.o.))Conclusion: The data obtained indicate that the EDSL has antidiarrhoeal and antiperistalsis activities and thus supports its traditional use. The data also show that the plant material given p.o. may be safe and/or non-toxic in mice.
Nowadays, there are increasing numbers of studies about synthetic chemicals according to the supply demands of bioactive chemicals. The current study aims to investigate genotoxic potential of bioactive synthetic pyridine compounds, phenyl-3-pyridinylmethanone (1), p-tolyl-3-pyridinylmethanone (2), and 4-methoxyphenyl-3-pyridinylmethanone (3), using Ames/Salmonella and Escherichia coli WP2 bacterial reversion mutagenicity test systems. The mutant bacterial tester strains sodium azide-sensitive Salmonella typhimurium TA1535, 9-aminoacridine-sensitive S. typhimurium TA1537, and N-methyl-N'-nitro-N-nitrosoguanidine-sensitive E. coli WP2uvrA were used to detect the mutagenic potential of the test compounds. The results indicated that none of the test substances showed significant mutagenic activity on S. typhimurium TA1535, TA1537, and E. coli WP2uvrA bacterial strains up to 1 µg/plate concentrations.
In bones, osteoblasts are responsible for bone formation. The cell death of osteoblasts may cause a series of bone diseases and lead to bone loss, such as osteoarthrosis, hyperparathyroidism, and Paget’s disease. Reactive oxygen species (ROS) are reported as a main factor for osteoblast cell death and further several bone diseases. However, the detailed mechanism is still largely unknown. Here, we found that ROS could induce cell death of rat osteoblast-like cell line ROS 17/2.8 via Akt (protein kinase B). Also, the mammalian target of rapamycin signaling was involved in this process. Our findings could help to reveal the cellular mechanism of osteoblast cell death, which is served for the pursuit of clinical treatment targets of relative bone diseases.
Epidemiological studies demonstrated that the exposure of different air pollutants including particulate matter (PM) has been related to adverse effect on immune system. Current study was designed to investigate cytokines in blood plasma of adolescent persons continuously exposed to different degrees of ambient air pollutions. Tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), IL-12p40, and IL-10 were chosen as cytokines of proinflammatory and anti-inflammatory immune response. The peripheral venous blood was taken from adolescents living in the cities of Stara Zagora region, Southeast Bulgaria, that is, in Stara Zagora, Kazanlak, and Chirpan. The quantity of cytokines in plasma samples was determined by enzyme-linked immunosorbent assay. Results demonstrated that youths living in Stara Zagora showed significantly smaller quantity of TNF-α, compared with adolescents from Kazanlak and Chirpan. Moreover, adolescents living in Stara Zagora showed significantly higher quantity of IL-10 than students from Kazanlak and Chirpan. Analysis of the data of air quality gives reason to assert that PM10 and PM2.5 have been the main atmospheric pollutants around the monitoring points. The complex air quality assessment based on these criteria determined that the highest air pollution was in the city of Stara Zagora, followed by Chirpan and the relatively unpolluted town was Kazanlak. We concluded that air pollutants, mostly PM2.5, can modulate cytokine production and can change the balance between proinflammatory TNF-α and anti-inflammatory IL-10 production. Increased levels of IL-10 combined with decreased level of TNF-α in adolescents living in Stara Zagora can serve as a biomarker for suppression of T helper 1 (Th1) cell-mediated immunity and exacerbation of Th2 humoral immune response and could be a prerequisite for the development of allergic and autoimmune diseases.
The synthetic organic compound 4-nonylphenol (4-NP) has been shown to have a wide range of adverse effects on the endocrine system of various animals including fish. The present study evaluated the potential effects of 4-NP on vitellogenin (VTG) synthesis, steroid, and thyroid hormone concentrations in both juvenile male and female rainbow trout (Oncorhynchus mykiss). Fish were exposed by intraperitoneal injection to different doses of 4-NP (1, 10, 50, and 100 μg g-1) or vehicle (coconut oil) over a period of 14 days. Blood samples were collected 7 and 14 days after initiation of treatment. Plasma VTG levels in 4-NP-treated fish were detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis as a high molecular weight protein band of 180 KDa. In addition, plasma VTG concentrations were quantified indirectly using plasma alkali-labile phosphate (ALP) and plasma calcium. Both ALP and calcium levels in plasma showed similar and parallel increase patterns after exposure to 4-NP that were significantly higher compared with controls. The analysis of plasma sex steroid levels revealed a significant increase in 17β-estradiol and testosterone in plasma of juvenile males and females, respectively. Furthermore, a significant increase was observed in plasma cortisol levels. On the other hand, 4-NP decreased both plasma triiodothyronine and thyroxine after 7 and 14 days of treatment. These results suggest that 4-NP can affect different parts of the endocrine system, which may lead to serious impairments in physiological homeostasis of juvenile rainbow trout.
Over recent years, nanotoxicology and the potential effects on human body have grown in significance, the potential influences of nanosized materials on the central nervous system have received more attention. The aim of this study was to determine whether zinc oxide (ZnO) nanoparticles (NPs) exposure cause alterations in emotional behavior and trace elements homeostasis in rat brain. Rats were treated by intraperitoneal injection of ZnO NPs (20–30 nm) at a dose of 25 mg/kg body weight. Sub-acute ZnO NPs treatment induced no significant increase in the zinc content in the homogenate brain. Statistically significant decreases in iron and calcium concentrations were found in rat brain tissue compared to control. However, sodium and potassium contents remained unchanged. Also, there were no significant changes in the body weight and the coefficient of brain. In the present study, the anxiety-related behavior was evaluated using the plus-maze test. ZnO NPs treatment modulates slightly the exploratory behaviors of rats. However, no significant differences were observed in the anxious index between ZnO NP-treated rats and the control group (p > 0.05). Interestingly, our results demonstrated minimal effects of ZnO NPs on emotional behavior of animals, but there was a possible alteration in trace elements homeostasis in rat brain.
Nitrobenzene is a carcinogen, which induces—among others—thyroid tumors. Melatonin is an effective antioxidant, whereas some antioxidative effects of propylthiouracil (PTU; an antithyroid medication used for the treatment of thyrotoxicosis) were also found. The aim of the study was to compare protective effects of melatonin and PTU against lipid peroxidation in homogenates of porcine thyroids, incubated in the presence of nitrobenzene.
Homogenates of porcine thyroids were incubated for 30 min in the presence of nitrobenzene (0.001, 0.01, 0.1, 0.25, 0.5, 1.0, 2.5, 5.0, 7.5, and 10.0 mM). The level of lipid peroxidation products (malondialdehyde + 4-hydroxyalkenals) was measured spectrophotometrically. Nitrobenzene (7.5 and 10.0 mM) increased lipid peroxidation in the homogenates of porcine thyroids. Subsequently, homogenates of porcine thyroids were incubated for 30 min in the presence of nitrobenzene (7.5 mM) plus one of the antioxidants: melatonin (0.000001, 0.00001, 0.0001, 0.001, 0.01, 0.1, 0.25, 0.5, 1.0, 2.5, 5.0, and 7.5 mM) or PTU (0.01, 0.1, 0.25, 0.5, 1.0, 2.5, 5.0, and 7.5 mM).
Lipid peroxidation caused by nitrobenzene was effectively prevented by melatonin, with the lowest effective concentration of 0.0001 mM, being only two orders of magnitude higher than physiological blood concentration in humans. At the same time, PTU revealed protective effects only in the highest used concentration (7.5 mM), which is practically never reached during pharmacological treatment in patients with thyrotoxicosis.
Melatonin can serve as an effective agent in protection against nitrobenzene-induced lipid peroxidation in porcine thyroid.
Copper (Cu) in trace amounts is essential for biological organisms. However, dysregulation of the redox-active metal has been implicated in different neurological disorders such as Wilson’s, Menkes’, Alzheimer’s, and Parkinson’s diseases. Since many households use Cu tubing in the plumbing system, and corrosion causes the metal to leach into the drinking water, there may be adverse effects on the central nervous system connected with low-level chronic exposure. The present study demonstrates that treatment with a biologically relevant concentration of Cu for 3 months significantly increases activation of the redox-modulated transcription factor AP-1 in mouse brains. This was independent of an upstream kinase indicated in AP-1 activation. Another redox-active transcription factor, NF-B, was not significantly modified by the Cu exposure. These results indicate that the effect of Cu on AP-1 is unique and may involve direct modulation of DNA binding.
Most of the fatal cases of mushroom poisoning are caused by Amanita phalloides. The amount of toxin in mushroom varies according to climate and environmental conditions. The aim of this study is to measure α-, β-, and -amanitin with phalloidin and phallacidin toxin concentrations. Six pieces of A. phalloides mushrooms were gathered from a wooded area of Düzce, Turkey, on November 23, 2011. The mushrooms were broken into pieces as spores, mycelium, pileus, gills, stipe, and volva. α-, β-, and -Amanitin with phalloidin and phallacidin were analyzed using reversed-phase high-performance liquid chromatography. As a mobile phase, 50 mM ammonium acetate + acetonitrile (90 + 10, v/v) was used with a flow rate of 1 mL/min. C18 reverse phase column (150 x 4.6 mm; 5 µm particle) was used. The least amount of -amanitin toxins was found at the mycelium. The other toxins found to be in the least amount turned out to be the ones at the spores. The maximum amounts of amatoxins and phallotoxin were found at gills and pileus, respectively. In this study, the amount of toxin in the spores of A. phalloides was published for the first time, and this study is pioneering to deal with the amount of toxin in mushrooms grown in Turkey.
The present study was designed to investigate the antinociceptive effects of methanolic leaf extract of Swietenia mahagoni (MESM) on acrylamide-induced painful neuropathy in rats. The intraperitoneal administration of acrylamide (30 mg/kg; for 24 consecutive days) has been employed for the induction of painful neuropathy. Acrylamide induced nociceptive pain sensitive changes, which have been assessed by hot plate, Von Frey Hair, and tail immersion tests at different time intervals, that is, 0, 6, 12, 18, and 24th day. Furthermore, the biochemical changes, that is, thiobarbituric acid-reactive substances, reduced glutathione, and total calcium levels have been estimated in sciatic nerve tissue on 24th day and histopathological changes have been observed in sciatic nerve tissue sample. MESM and pregabalin have been administered for 14 consecutive days before 1 h of the each acrylamide injection. Administration of acrylamide resulted in significant changes in behavioral and biochemical parameters. Pretreatment of MESM ameliorated acrylamide-induced behavioral, biochemical, and histopathological changes in a dose-dependent manner, which is similar to that of pregabalin-pretreated group. These findings suggested that the neuroprotective effect of S. mahagoni may be due to its potential of antioxidative, calcium channel modulatory, and neuroprotective action.
The aim of the study was to investigate the influence of occupational lead (Pb) exposure on lipid peroxidation, protein carbonylation, and plasma viscosity in workers. The examined group included 283 healthy male employees of manufacturing facilities using zinc and Pb. The mean blood concentrations of Pb and zinc protoporphyrin as well as the mean urine -aminolevulinic acid levels were used as markers of exposure for the examined group. Taking into account the obtained mean values of blood lead level, the examined group was divided into three subgroups. When comparing the control group with the subgroups, Pb exposure markers were significantly elevated in all the three subgroups. Concentrations of conjugated dienes (CD), lipid hydroperoxides, malondialdehyde (MDA), and protein carbonyl groups were also significantly increased. Conversely, the levels of total protein and protein sulfhydryls were significantly decreased in the subgroups compared with the controls. The plasma viscosity was significantly elevated in the subgroups. A dose–response between Pb levels and plasma viscosity was not observed. Pb supposedly elevates MDA and CD in a dose-dependent manner. In conclusion, occupational Pb exposure induces oxidative stress that results in lipid and protein damage. Moreover, Pb-induced oxidative stress is likely the primary factor that elevates plasma viscosity, despite decreased protein levels.
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Mercury, one of the most toxic heavy metals, is ubiquitous in environment. The adverse health impact of mercury on living organisms is well known. The health care facilities are one of the important sources of mercury release into the atmosphere as mercury items are extensively used in hospitals. To assess the awareness about mercury toxicity and the knowledge of proper handling and disposal of mercury-containing items in health care set–up, a questionnaire-based survey was carried out amongst doctors (n = 835), nurses (n = 610) and technicians (n = 393) in government hospitals, corporate hospitals and primary health care centres in the Indian states of Delhi, Uttar Pradesh and Haryana. The study was conducted using a tool-containing pretested structured multiple-choice questionnaire. Analysis of the results using STATA 11.1 software highlighted that overall awareness was more in corporate sector. However, percentage range of knowledge of respondents irrespective of health care sector was only between 20 and 40%. Despite the commitment of various hospitals to be mercury free, mercury containing-thermometer/sphygmomanometer are still preferred by health professionals. The likely reasons are availability, affordability, accuracy and convenience in use. There is an urgent need for source reduction, recycling and waste minimization. Emphasis must be laid on mercury alternative products, education and training of health personnel and public at large, about correct handling and proper clean up of spills.
Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease. The present study was undertaken to investigate the pretreatment effects of standardized Ginkgo biloba extract (EGb761®) and low-dose whole-body -irradiation on the neurological dysfunction in the reserpine model of PD. Male Wistar rats were pretreated orally with EGb761 or fractionated low-dose whole-body -irradiation or their combination, then subjected to intraperitoneal injection of reserpine (5 mg/kg body weight) 24 h after the final dose of EGb761 or radiation. Reserpine injection resulted in the depletion of striatal dopamine (DA) level, increased catalepsy score, increased oxidative stress indicated via depletion of glutathione (GSH), increased malondialdehyde (MDA) and iron levels, decreased DA metabolites metabolizing enzymes; indicated by inhibition by glutathione-S-transferase, and nicotinamide adenine dinucleotide phosphate (NADPH)-quinone oxidoreductase (NQO) activities, mitochondrial dysfunction; indicated by declined complex I activity, and adenosine triphosphate (ATP) level and increased apoptosis; indicated by decreased mitochondrial B cell lymphoma-2 (Bcl-2) protein level and by transmission electron microscope. EGb761 and low-dose -radiation ameliorated the reserpine-induced state of oxidative stress, mitochondrial dysfunction, and apoptosis in brain. It can be concluded that EGb761, a widely used herbal medicine and low dose of -irradiation have protective effects for combating Parkinsonism possibly via replenishment of GSH levels.
The freshwater carp, Cyprinus carpio, was exposed to 0.5 mg (30% of median lethal concentration (LC50)), 1.0 mg (60% of LC50), and 1.6 mg (LC50) of dithiopyridine herbicide per liter for acute (24 h) and 1/10 of LC50 (0.2 mg/L/day) for sublethal (1, 3, 7, 14, and 21 days) experiments. The herbicide bioaccumulation was significantly affected by the acute exposure levels and the experimental periods and was positively correlated with them. One-way analysis of variance revealed that the acute and sublethal exposure to the herbicide as well as the experimental periods caused significant reduction in the concentrations of catecholamines (dopamine (DA) and norepinephrine (NE)), elevation of acetylcholine (ACh), and was associated with a marked decrease in the activity of acetylcholinesterase (AChE). In comparison with the corresponding controls, most levels of the DA and NE and the activity of AChE were significantly decreased, whereas the concentration of ACh was markedly elevated, during acute and sublethal exposure. In the acute and sublethal experiments, the herbicide accumulated in the brain was inversely proportional to the levels of DA and NE and the activity of AChE but has a direct correlation with the concentration of ACh. In addition, the brain’s AChE activity was negatively correlated with ACh content during the acute (r = -0.94) and sublethal (r = -0.78) experiments.
The present study was carried out to evaluate the neuroprotective effect of quercetin (QE) in protecting the cadmium (Cd)-induced neuronal injury in frontal cortex of rats. A total of 30 adult male Sprague-Dawley rats were randomly divided into three groups of 10 animals each: control, Cd treated and Cd treated with QE. The Cd-treated group was injected subcutaneously with cadmium chloride (CdCl2) dissolved in saline at a dose of 2 ml/kg/day for 30 days, resulting in a dosage of 1 mg/kg Cd. The rats in QE-treated groups were given QE (15 mg/kg body weight) once a day intraperitoneally starting 2 days prior to Cd injection, during the study period. Rats were sacrificed at the end of the study and the frontal cortex tissues were removed for biochemical and histopathological investigation. To date, there is no available information on the effect of QE on neuronal injury after Cd exposure. Rats intoxicated with Cd for 30 days, significantly increased tissue malondialdehyde (MDA) levels and significantly decreased enzymatic antioxidants superoxide dismutase, glutathione peroxidase and catalase in the frontal cortex tissue. Administration of QE with Cd significantly diminished the levels of MDA and significantly elevated the levels of enzymatic antioxidants in the frontal cortex tissue. The histopathological studies in the brain of rats also supported that QE markedly reduced the Cd-induced histopathological changes and well preserved the normal histological architecture of the frontal cortex tissue. The caspase-3 immunopositivity was increased in degenerating neurons of the Cd group. Treatment with QE markedly reduced the immunoreactivity of degenerating neurons. In conclusion, the results of the current study suggest that QE may be beneficial in combating the Cd-induced neurotoxicity in the brain of rats. We believe that further preclinical research into the utility of QE may indicate its usefulness as a potential treatment for neurodegeneration after Cd exposure in rats.
The present study was aimed to investigate the effects of subacute and subchronic treatment of some plant growth regulators (PGRs), such as abscisic acid (ABA) and gibberellic acid (GA3), on neurological and immunological biomarkers in various tissues of rats. The activities of acetylcholinesterase (AChE) and butrylcholinesterase (BChE) were selected as biomarkers for neurotoxic biomarkers. Adenosine deaminase (ADA) and myeloperoxidase (MPO) were measured as indicators for immunotoxic investigation purpose. Wistar albino rats were orally administered with 25 and 50 ppm of PGRs ad libitum for 25–50 days continuously with drinking water. The treatment of PGRs caused different effects on the activities of enzymes. Results showed that the administrations of ABA and GA3 increased AChE and BChE activities in some tissues of rats treated with both the dosages and periods of ABA and GA3. With regard to the immunotoxic effects, ADA activity fluctuated, while MPO activity increased after subacute and subchronic exposure of treated rat tissues to both dosages when compared with the controls. The observations presented led us to conclude that the administrations of PGRs at subacute and subchronic exposure increased AChE, BChE, and MPO activities, while fluctuating the ADA activity in various tissues of rats. This may reflect the potential role of these parameters as useful biomarkers for toxicity of PGRs.
This study was aimed at investigating alterations in renal and hepatic toxicity induced by exposing to a combination of three solvents, namely, benzene, toluene and xylene in adult mice. The mice were divided into three groups (control, low-dose-treated (450 ppm) and high-dose (675 ppm) groups) using randomization methods. The treated groups were exposed to vapours of a mixture of benzene, toluene and xylene at doses of 450 and 675 ppm, for 6 h day-1 for a short-term of 7-day exposure period. The study revealed that the solvent exposure resulted in an increase in the weight of liver and kidney as compared to the control. Biochemical analyses indicated a significant decline in the activities of superoxide dismutase and catalase in both the treated groups, with concomitant increase in lipid peroxidation. Liver aminotransferases (alanine aminotransferase and aspartate aminotransferase) were elevated with significant alterations in the levels of protein, creatinine and cholesterol in these tissues upon solvent exposure. Correlated with these changes, serum thyroid hormones T3 and T4 were also significantly altered. This study, therefore, demonstrates that inhalation of vapours from the solvent mixture resulted in significant dose-dependent biochemical and functional changes in the vital tissues (liver and kidney) studied. The study has specific relevance since humans are increasingly being exposed to such solvents due to increased industrial use in such combinations.
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We analyzed the aspects of lethality, genotoxicity, and cytotoxicity in the ten spotted live-bearer exposed under laboratory conditions to the pirimicarb-based formulation Patton Flow® (50% active ingredient (a.i.)). Acute effects were evaluated using different end points for lethality, genotoxicity, and cytotoxicity. Median lethal concentration (LC50) estimation was employed as a bioassay for lethality, whereas micronucleus (MN) induction and alterations in erythrocyte/erythroblast frequency were used as end points for genotoxicity and cytotoxicity, respectively. Results demonstrated an LC5096h value of 88 mg/L. Patton Flow® increased the MN frequency in fish erythrocytes after 48 h of exposure at a concentration of 66 mg/L, whereas a concentration range of 22–66 mg/L was able to exert the same genotoxic effect at 96 h of treatment. Furthermore, cytotoxicity was also observed by alterations in erythrocyte/erythroblast frequencies within the concentration range of 22–66 mg/L, regardless of the exposure time. Our current observations provide evidence that Patton Flow® (50% a.i.) should be considered a clear lethal, cytotoxic, and genotoxic agent on Cnesterodon decemmaculatus. Thus, repeated applications of this carbamic insecticide can enter the aquatic environment and exert deleterious effects on aquatic organisms other than the evaluated species C. decemmaculatus.
In this research, the mathematical models, indicating the capability of various units, such as rapid mixing, coagulation and flocculation, sedimentation, and the rapid sand filtration are used. Moreover, cost functions were used for the formulation of conventional water and wastewater treatment plant by applying Clark’s formula (Clark, 1982). Also, by applying dynamic programming algorithm, it is easy to design a conventional treatment system with minimal cost. The application of the model for a case reduced the annual cost. This reduction was approximately in the range of 4.5–9.5% considering variable limitations. Sensitivity analysis and prediction of system’s feedbacks were performed for different alterations in proportion from parameters optimized amounts. The results indicated (1) that the objective function is more sensitive to design flow rate (Q), (2) the variations in the alum dosage (A), and (3) the sand filter head loss (H). Increasing the inflow by 20%, the total annual cost would increase to about 12.6%, while 20% reduction in inflow leads to 15.2% decrease in the total annual cost. Similarly, 20% increase in alum dosage causes 7.1% increase in the total annual cost, while 20% decrease results in 7.9% decrease in the total annual cost. Furthermore, the pressure decrease causes 2.95 and 3.39% increase and decrease in total annual cost of treatment plants.
Objective: To investigate the antioxidant role in reversing cytogenetic changes
caused by solvent exposure in paint industry.
Subjects and Methods: A prospective controlled clinical trial was performed on 39
workers exposed to solvents and 39 workers not exposed to solvents by supplying
a mixture of antioxidant vitamins (A, C, E and selenium) and the after effects
of such regimen were analyzed. Environmental monitoring was carried out for air
concentrations of different solvents at workplace. Exposed group was
cytogenetically tested before and after giving the mixture of antioxidant
vitamins for 1 month duration.
Results: Frequency of chromosomal aberrations (CAs) and the mean of sister
chromatid exchanges (SCEs) were statistically significantly higher among exposed
workers than among controls. After the supplementation of antioxidants, there
was a statistically significant decrease in the frequency of CAs, and 88%
abnormal levels of SCEs were back to normal levels.
Conclusion: Antioxidant supplementation decreases the frequency of CAs and SCEs
among exposed workers.
Aluminum (Al) is a nonessential, toxic element to which humans are constantly exposed as a result of an increase in industrialization and improving technology practices. The aim of the study was to investigate the effects of different durations and doses of Al exposure on serum and tissue element levels and erythrocyte osmotic fragility in rats. A total of 40 male Wistar Albino rats were divided into five groups: control, group I (3 weeks, 8 mg/kg), group II (6 weeks, 8 mg/kg), group III (3 weeks, 16 mg/kg), and group IV (6 weeks, 16 mg/kg). Al chloride (AlCl3) was injected intraperitoneally (i.p.) five times a week. At the end of the experimental period, levels of Al, iron (Fe), copper (Cu), and zinc (Zn) in serum, liver, and kidney tissues were measured using inductively coupled plasma optical emission spectrometry. Osmotic fragility was determined using a spectrophotometer. The results of the experiment indicate that Al induced a statistically significant increase in Al and Fe concentrations in liver and serum as well as in Cu in the kidney. The Fe concentration in serum and kidney tissues was significantly lower in all the groups. As a result of our study, it may be concluded that tissue Al accumulation may lead to an increase in osmotic fragility of erythrocytes and abnormal trace element levels.
Occupational exposure to hexavalent chromium (Cr(VI)) compounds is of concern in many Cr-related industries and their surrounding environment. Cr(VI) is a proven toxin and carcinogen. The Cr(VI) compounds are easily absorbed, can diffuse across cell membranes, and have strong oxidative potential. Despite intensive studies of Cr(VI) pro-oxidative effects, limited data exist on the influence of Cr(VI) on selenoenzymes thioredoxin reductase (TrxR) and glutathione peroxidase (GPx)—important components of antioxidant defense system. This study investigates the effect of Cr(VI) exposure on antioxidant defense status, with focus on these selenoenzymes, and on trace element homeostasis in an acute experiment in rat. Male Wistar rats (130–140g) were assigned to two groups of 8 animals: I. control; and II. Cr(VI) treated. The animals in Cr(VI) group were administered a single dose of K2Cr2O7 (20 mg /kg, intraperitoneally (ip)). The control group received saline solution. After 24 h, the animals were sacrificed and the liver and kidneys were examined for lipid peroxidation (LP; thiobarbituric acid reactive substances (TBARS) concentration), the level of reduced glutathione (GSH) and the activities of GPx-1, TrxR-1, and glutathione reductase (GR). Samples of tissues were also used to estimate Cr accumulation and alterations in zinc, copper, and iron levels. The acute Cr(VI) exposure caused an increase in both hepatic and renal LP (by 70%, p < 0.01 and by 15%, p < 0.05, respectively), increased hepatic GSH level and GPx-1 activity, and decreased renal GPx-1 activity. The activity of GR was not changed. A significant inhibitory effect of Cr(VI) was found on TrxR-1 activity in both the liver and the kidneys. The ability of Cr(VI) to cause TrxR inhibition could contribute to its cytotoxic effects. Further investigation of oxidative responses in different in vivo models may enable the development of strategies to protect against Cr(VI) oxidative damage.
In the present study, we evaluated the pharmacological and toxicological effects of Teucrium stocksianum. The crude extract of T. stocksianum (Ts.Cr) and its subsequent organic fractions: n-hexane (Ts.Hex), chloroform (Ts.CHCl3) and ethyl acetate (Ts.EtAc) exhibited 1,1-diphenyl,2-picrylhydrazyl free radical scavenging activity with different potencies. Ts.EtAc was found to be most potent. Ts.Cr, Ts.Hex, Ts.CHCl3 and Ts.EtAc showed significant bactericidal activity against Escherichia coli, Staphylococcus aureus, Salmonella typhi, Shigella flexneri and Bacillus subtilis at their extent. Ts.Cr, Ts.Hex, Ts.CHCl3 and Ts.EtAc displayed fungicidal action against Aspergillus niger, Aspergillus flavus, Aspergillus fumigatus and Fusarium solani at various minimum inhibitory concentrations. Ts.Cr and Ts.EtAc exhibited marked inhibition of Leishmania tropica growth, observed after 48 and 96 hrs of treatment. These data indicate that the T. stocksianum methanolic extract and its resultant fractions possess antioxidant, antibacterial, antifungal and antileishmanial activities. Thus, the present research unearths the scientific base for T. stocksianum medicinal application as antioxidant and antimicrobial agents.
Organophosphate (OP) compounds are the most commonly used pesticide groups and they are commercially used in the market for local and industrial purposes. Paraoxonase 1 (PON1) enzyme plays an important role in biotransformation of OP compounds, which shows toxic effects via inhibiting the acetylcholinesterase (AChE). The aim of this study was to determine the effects of PON1 gene polymorphism and its effects on PON and AChE enzyme activities in individuals who were exposed to organophosphorus insecticides due to occupational reasons, and to profile the probability of susceptibility to organophosphorus compounds. For this purpose, 54 individuals who were exposed to OPs and 54 healthy unrelated controls were studied. First, PON1 and AChE enzyme activities were measured. Second, PON1 192 Q/R polymorphism was determined by standard polymerase chain reaction–restriction fragment length polymorphism technique. When the PON1 192 Q/R polymorphism was compared with PON1 enzyme activities, statistically significant association was found in both OP-exposed and control groups (p < 0.05). PON1 192 R(+) (QR + RR genotypes) genotype carriers had higher PON1 activities than 192 R(-) (QQ) genotype carriers. On the other hand, results were statistically analyzed in terms of AChE enzyme activities and there were statistically significant differences only in the OP-exposed group (p < 0.05). The mean AChE concentration in the OP-exposed group was determined as 33.79 ± 6.84 U/g haemoglobin (Hb) for PON1 192 R(+) carriers and 30.37 ± 7.62 U/g Hb for PON1 192 R(+) carriers. As a conclusion, PON1 and AChE activities were increasing according to the genotypes found in individuals having been exposed to OPs at a chronic level; 192 R(+) > 192 R(-), respectively.
Ziprasidone, an atypical antipsychotic agent, has been shown to increase the corrected QT (QTc) interval in some patients. The aim of this study was to reveal the effects of metoprolol and diltiazem on ziprasidone drug-induced prolonged QTc interval. A total of 24 rats were equally divided into the following four groups: the first group was used as the control and received 1 mL/kg saline; 3 mg/kg ziprasidone and saline were administered to the second group; 3 mg/kg ziprasidone and 1 mg/kg metoprolol were administered to the third group and 3 mg/kg ziprasidone and 2 mg/kg diltiazem were administered to the fourth group. Two hours following application of the drugs, the QTc was calculated by performing electrocardiography in derivation (D)I. The duration of QTc interval was compared among the four groups. The mean QTc intervals were significantly increased in the third and fourth groups compared with the second group (p < 0.0005 and p < 0.0001, respectively). The study demonstrated the effectiveness of metoprolol and diltiazem in the prevention of ziprasidone-induced elongation in the QTc interval. Both metoprolol and diltiazem may be considered in the prophylactic therapy of high-risk patients who are using ziprasidone.
It has been reported that a leukotriene (LT)-D4 receptor (i.e. cysteinyl LT1 receptor; CysLT1R) has an important role in carcinogenesis. The current study was carried out to assess the possible antitumor effects of montelukast (MON), a CysLT1R antagonist, in a mouse mammary carcinoma model, that is, a solid Ehrlich carcinoma (SEC). Effects of MON on tumor-induced immune dysfunction and the possibility that MON may modulate the antitumor and immunomodulatory effects of doxorubicin (DOX) were also studied. The effects in tumor-bearing hosts of several dosings with MON (10 mg/kg, per os), with and without the added presence of DOX (2 mg/kg, intraperitoneal), were investigated in vivo; end points evaluated included assessment of tumor volume, splenic lymphocyte profiles/functionality, tumor necrosis factor-α content, as well as apoptosis and expression of nuclear factor-B (NF-B) among the tumor cells. The data indicate that MON induced significant antitumor activity against the SEC. MON treatments also significantly mitigated both tumor- and DOX-induced declines in immune parameters assessed here. Moreover, MON led to decreased NF-B nuclear expression and, in doing so, appeared to chemosensitize these tumor cells to DOX-induced apoptosis.
In this research, we aimed to determine genotoxic effects of boron (B) and zinc (Zn) on Zea mays by using total soluble protein content and random amplification of polymorphic DNA (RAPD) analyses. For the RAPD analysis, 16 RAPD primers were found to produce unique polymorphic band profiles on treated maize seedlings. With increased Zn and B concentrations, increased polymorphism rate was observed, while genomic template stability and total soluble protein content decreased. The treatment with Zn was more effective than that of B groups on the levels of total proteins. The obtained results from this study revealed that the total soluble protein levels and RAPD profiles were performed as endpoints of genotoxicity and these analyses can offer useful biomarker assays for the evaluation of genotoxic effects on Zn and B polluted plants.
Aim: Present study was conducted to evaluate the dermatoprotective effects of plant extracts (Ficus religiosa, Ficus benghalensis, and Ficus racemosa) against known irritants such as sodium dodecyl sulfate (SDS), atrazine, and petrol. Methods: The study was conducted in adult male rabbits. Ethanol extracts of plants were obtained through Soxhlet. All irritants and Ficus extracts were topically applied to the backs of rabbits daily for 4 days, while pure ethanol served as control. Skin was examined after 24, 48, and 96 h for erythema. Skin biopsies were taken on 5th day for microscopic examination. Results: Erythema produced by irritants reduced significantly with the simultaneous application of Ficus extracts. The mean ± SEM epidermal thickness (micrometer) with SDS was 45.40 ± 1.89, F. religiosa + SDS was 18.60 ± 0.51, F. benghalensis + SDS was 18.40 ± 0.25, F. racemosa + SDS was 18.80 ± 0.37, and mixture of three Ficus species + SDS was 16.80 ± 0.37. Similar findings were revealed after using plant extracts with atrazine and petrol. The mean ± SEM epidermal layer count for SDS was 3.60 ± 0.25, atrazine was 3.40 ± 0.25, petrol was 3.40 ± 0.25, and ethanol (control) was 1.00 ± 0.20. This count reduced to 1.20 ± 0.20 for three Ficus species + SDS, 1.40 ± 0.25 for Ficus species + atrazine, and 1.40 ± 0.25 for Ficus species + petrol. Conclusion: Ficus species demonstrated the potential to block the dermatotoxic effects of topical irritants and could be used successfully to prevent skin toxicity.
Wogonin is a flavonoid compound which exhibits antioxidation, anti-inflammation, neuroprotection, and antitumorgenesis functions. However, the mechanism of how wogonin reduces proinflammatory cytokine generation in activated microglia is unclear. At present, we found wogonin inhibited lipopolysaccharide (LPS)-/interferon- (INF-)-induced generation of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Wogonin exhibited parallel inhibition on LPS-/INF--induced expression of IL-6 and TNF-α messenger RNA at the same concentration range. LPS-/INF--induced phosphorylation of signal transduction and transcription 1 and 3 (STAT1/3) were also inhibited by wogonin. Although wogonin expressed only weak inhibitory effect on LPS-/INF--induced phosphorylation of Janus kinase-2 (Jak-2) and tyrosine kinase (Tyk)-2, it significantly attenuated the phosphorylation of Jak-1 and Jak-3. These results indicated that the blockade of IL-6 and TNF-α production by wogonin in LPS-/INF--stimulated BV2 microglial cells was attributed mainly to the interference in Jak-1/-3-STAT1/3 signaling pathway.
For ages, lichens have long been investigated popularly for biological roles, mainly antitumor, antimicrobial and antioxidant activities. Many positive results were obtained in these previous research. Thus, in this study, we aimed to determine whether extracts of Usnea articulata (UAE) and Usnea filipendula (UFE) possessing a protection against aflatoxin B1 (AFB1)-induced genotoxic and oxidative damage. The results of our studies showed that 5 μM concentrations of AFB1 increased the frequencies of sister chromatid exchange (SCE) and the level of malondialdehyde (MDA) and decreased the activities of superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GPx). However, when 5, 10 and 20 µg/mL concentrations of UAE and UFE was added to AFB1, the frequencies of SCE and MDA level were decreased and SOD, GSH and GPx level were increased. The Ames (Salmonella typhimurium TA1535, TA1537) and WP2 (Escherichia coli) test systems carried out evinced that UAE and UFE possess any mutagenicity, but have antimutagenic effects. Consequently, the results of this experiment have clearly shown that UAE and UFE have strong antioxidative and antigenotoxic effects that are associated with its antioxidant nature. A detailed study can be performed to determine the antioxidant properties of each compound that will extend the use of lichen extracts in food and pharmacy industries.
The objective of the current study was to investigate the potential oxidative damage of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in hepatic microsomal fractions in vitro and to further elucidate the potential modulatory effect of lycopene. Rat liver microsomes were divided into four groups. Group I served as a control and is incubated with vehicle (toluene). Groups II and IV were incubated with 20 µM lycopene for 1 h before further incubating; groups III and IV with 15 nM of TCDD for further 1 h. Hydrogen peroxide (H2O2) production, lipid peroxidation (LPO), protein carbonyl content and activities of uridine 5'-diphospho-glucuronyltransferase (UDPGT) and P450 were significantly increased. Moreover, the activity of antioxidant enzymes superoxide dismutase, glutathione peroxidase, catalse, glutathione-S-transferase and glutathione reductase as well as the microsomal thiol content were significantly decreased. Incubation with lycopene (group IV) maintained near normal activities of the enzymes, normalized thiol and carbonyl content and significantly reduced LPO and H2O2 production. In conclusion, the findings of the study indicate that TCDD induces a significant oxidative stress in liver microsomes as manifested by increased LPO, H2O2 production, protein carbonyl content and activities of UDPGT and P450 and decreased antioxidant enzymes activities and thiol content. By the reversal of biochemical and oxidative markers toward normalcy, the protective role of lycopene is illuminated in rat liver microsomal toxicity.
Purpose: To investigate the current status of exposure to mercury (Hg) among dental health workers in Turkey. Methods: A total of 115 persons working in the same hospital were included in the study and were divided into three groups. Group 1 consisted of 67 dentists; group 2 consisted of 21 dental personnel who work with amalgam, and group 3 consisted of 27 control subjects who work in the same hospital but are non-dental personnel. The number of amalgam fillings that have been made by the dentists and the number of own fillings of the subjects were recorded. Results: Plasma Hg levels were found to be 3.76 ± 1.84, 3.54 ± 1.83, and 2.69 ± 0.97 µg/L in groups 1, 2, and 3, respectively. Hg concentrations in group 1 were significantly higher than the control group. There was no significant difference between groups 1 and 2. The number of amalgam fillings made by the dentists in the previous year correlated significantly with plasma Hg levels (r = 0.378, p < 0.01). There was no significant correlation between the own amalgam fillings in the teeth of the subjects and Hg levels. Conclusion: Preventive measures for protection from exposure to Hg are necessary for occupational health in dentistry and proper industrial hygiene rules should be emphasized to avoid contamination during work.
Purpose: Paraquat (PQ; 1,1'dimethyl-bipyridilium 4,4'-dichloride), which is used extensively throughout the world, is highly toxic to humans. We aimed to investigate the protective effects of different doses of caffeic acid phenethyl ester (CAPE) on PQ-intoxicated rats.Materials and methods:A total of 80 rats were divided into the following eight groups, comprising 10 rats in each group: group 1: control; group 2: administered with CAPE (10 µmol/kg); group 3: administered with 15 mg/kg PQ (PQ15 group); group 4: administered with 30 mg/kg PQ (PQ30 group); group 5: administered with 45 mg/kg PQ (PQ45 group); group 6: administered with 15 mg/kg PQ + CAPE; group 7: administered with 30 mg/kg PQ + CAPE and group 8: administered with 45 mg/kg PQ + CAPE. Both PQ and CAPE were injected intraperitoneally. Pancreatic tissue was examined with both haematoxylin and eosin and immunochemical staining.Results:The ratio of the immunohistochemical staining area to the total pancreatic area of the β cells revealed that statistically significant differences were observed only between the PQ and PQ + CAPE groups (p < 0.05). Discussion:The evaluation of the data suggests that CAPE can be used to prevent acute effects of PQ intoxication.
Sonchus asper is traditionally used in the treatment of renal dysfunction. In the present study, protective effects of S. asper against carbon tetrachloride (CCl4)-induced nephrotoxicity of rats were determined. In this study, 24 male albino rats (190–200 g) were equally divided into four groups. Group I (control group) was given saline (1 ml/kg body weight (b.w.), 0.85% NaCl) and dimethyl sulfoxide (1 ml/kg b.w.); group II was treated with CCl4 (1 ml/kg b.w. intraperitoneally); groups III and IV were administered with CCl4 and after 48 h with S. asper n-hexane extract (SHE; 100 and 200 mg/kg b.w.). All the treatments were given twice a week for 4 weeks. The results revealed that CCl4-induced oxidative stress as evidenced by the significant depletion of antioxidant enzymes, namely, superoxide dismutase, catalase, peroxidase, glutathione-S-transferase, glutathione peroxidase, glutathione reductase, and glutathione contents, while increased lipid peroxidation (thiobarbituric acid-reactive substances contents). Administration of SHE significantly ameliorated (p < 0.01) the activity of antioxidant enzymes and reduced lipid peroxides. Coadministration revealed that S. asper extract can protect the kidney against CCl4-mediated oxidative damage by restoring the activity of antioxidant enzyme, due to the presence of plant bioactive constituents.
This study was conducted to evaluate the efficacy of citrus fruit oil (CFO; 2.5 g kg-1) on the clinicopathological changes in broilers fed with diets containing 1 ppm of aflatoxin (AF). A total of 160 Ross 308 broiler chicks of 1-day-old were procured from a commercial hatchery, divided randomly on 7th day of age into four groups with two replicates of 20 birds each and fed with basal diet (group A), basal diet + CFO (group B), basal diet + AF (group C) and CFO + basal diet + AF (group D). The gross and histopathological changes in the liver, kidney, spleen, thymus and bursa of Fabricius were investigated and relative organ weights were calculated. Slight to moderate hydropic degeneration, fatty change with the formation of cyst in some cases, periportal necrosis, infiltration of heterophils and mononuclear cells and bile duct hyperplasia were observed in chicks fed with 1 ppm AF-containing diet. The addition of CFO to AF-containing diet moderately decreased the magnitude and severity of lesions (hydropic degeneration and bile duct hyperplasia) in the liver. The supplementation of CFO to the basal diet did not produce any adverse effects in birds.
Chemical materials are environmental contaminants, are extensively used in laboratories, and may cause various forms of health hazards in laboratory workers. Therefore, this toxicity most likely is a result of the oxidative metabolism of chemical to reactive products. As green tea (GT) possesses antioxidant effects, the objective of this study was to examine any amelioration oxidative stress in chemical laboratory workers drinking one cup (3 g/300 ml water) of freshly prepared tea once daily. Baseline characteristics including age, sex, smoking, fruit consumption, and duration of exposure were recorded via questionnaire to the subjects. Saliva level oxidative stress parameters such as total antioxidant capacity (TAC), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) were estimated before and after consumption of GT in these workers. Treatment of subjects with GT induced a significant reduction in saliva GPx activity (406.61 ± 22.07 vs. 238.96 ± 16.26 U/l p = 0.001) and induction in TAC (0.46 ± 0.029 μmol/ml vs. 0.56 ± 0.031, p = 0.016). No statistically significant alteration was found for saliva SOD (0.080 ± 0.0019 vs. 0.079 ± 0.0014, p > 0.05) and CAT (20.36 ± 0.69 vs. 19.78 ± 0.71, p > 0.05) after 28 days treatment by GT. These results demonstrate that drinking GT during chemical exposure can reduce several parameters indicative of oxidative stress. In conclusion, using GT as a dietary supplement can be a rational protocol to control source of hazards in chemical laboratory workers.
This study focused on two areas (Abu-Zaabal and El-Tal El-Kabir) of the Ismailia canal. The samples represented the effect of the factories’ effluent discharge onto the canal. Physical characteristics (water temperature and pH) and chemical characteristics (total hardness, dissolved oxygen, biological oxygen demand and chemical oxygen demand) were measured to identify the water quality in the two areas of the Ismailia canal. These measurements showed slight variations between the two stations. Additionally, the histological and histochemical analyses in the liver of Bagrus bayad fish samples were done. Histological studies of liver showed more severe degeneration in the fish samples of El-Tal El-Kabir station. Histochemical studies on protein and glycogen contents in the liver of B. bayad showed a progressive decrease in their staining intensity to bromophenol blue and periodic acid Schiff at two stations. This study, therefore, concludes that Ismailia canal water (Abu-Zaabal and El-Tall El-Kabir) stations create metabolic crisis and impairment in fish liver. The depletion in the levels of protein and glycogen points leads to the exhaustion of cell energy that is of high demand for fish during stressful conditions. Therefore, it is imperative for the authorities concerned to ensure that treated effluent discharge comply with acceptable standards to save our environment from destruction.
Both p16 and p15 proteins are inhibitors of cyclin-dependent kinases that prevent the cell going through the G1/S phase transaction. E-cadherin is a transmembrane glycoprotein that mediates calcium-dependent interactions between adjacent epithelial cells. Two groups of patients were selected: the first group suffered from epithelial serous ovarian tumors and the second group suffered from benign ovarian lesions; ovarian tissue samples from all the subjects (benign and malignant) were subjected to methylation-specific polymerase chain reaction for methylated and unmethylated alleles of the genes (E-cadherin, p15, and p16). Results obtained showed that aberrant methylation of p15 and p16 genes were detected in 64.29 and 50% of ovarian cancer patients, while E-cadherin hypermethylation was detected in 78.57% of ovarian cancer patients. Methylation of E-cadherin was significantly correlated with different stage of disease (p < 0.05). It was found that the risk of E-cadherin hypermethylation was 1.347-fold, while risk of p15 hypermethylation was 1.543-fold and p16 was 1.2-fold among patients with ovarian cancer than that among patients with benign ovarian lesions. In conclusion, Dysfunction of the cell cycle and/or the cell–cell adhesion molecule plays a role in the pathogenesis of ovarian cancer and that the analysis of the methylation of p15 and E-cadherin genes can provide clinically important evidence on which to base the treatment.
Direct-type catalytic Mannich reaction for the synthesis of β-aminoketones from cyclohexanone, substituted aromatic amines and aromatic or hetero-aromatic aldehydes has been applied in water with bismuth triflate under ultrasound. Good yields of the expected β-aminoketones were obtained from available substrates, at room temperature in 1–2 hours. This study was designed to evaluate the mutagenic and antimutagenic potential of synthesized β-aminoketones compounds using Ames/Salmonella and Escherichia coli WP2 bacterial reverse mutation assay systems.
In allelopathy, one plant suppresses the growth and development of other plant/plants by negatively affecting a variety of physiological and biochemical reactions. We checked the effects of methanolic extracts (allelochemical extracts) of Phytolacca latbenia (Moq.) H. Walter on antioxidant enzyme activities such as peroxidases (PODs), super oxide dismutases (SODs) and catalase (CAT) and on total protein contents (TPC), cellular injury (CI), and malondialdehyde (MDA) in the germinating seeds of Brassica napus L. (dicot) and Triticum aestivum L. (monocot). Both the crude methanolic extract root (CMER) and crude methanolic extract aerial (CMEA) of P. latbenia at 10000 ppm significantly reduced the POD activity in both the test seeds. The activity of SODs was significantly decreased by both CMER and CMEA in B. napus germinating seeds. A linear increase in the activity of CAT, CI, and MDA contents was found in both the test seeds with the increasing concentrations of CMEA and CMER, while TPC of the germinating seeds was found decreased. It is inferred that both the CMEA and CMER inhibited/delayed the seed germination, reduced the seedling growth by affecting a variety of biochemical and physiological attributes, and also caused cellular membrane injury in the germinating seeds of both the monocot and dicot seeds.
Mast cells play a vital role in hypersensitivity reactions. Rocuronium is known to cause mast cell mobilization, hypersensitivity, and pancreatitis. The aim of this study was to investigate the effects of sugammadex on pancreatic changes due to rocuronium. A total of 42 Sprague-Dawley male rats were divided into six equal groups to receive either rocuronium 1 mg/kg intravenously (i.v., R group), rocuronium 1 mg/kg + sugammadex 16 mg/kg i.v. (RS16 group), rocuronium 1 mg/kg + sugammadex 96 mg/kg i.v. (RS96 group), sugammadex 16 mg/kg (S16), sugammadex 96 mg/kg i.v. (S96 group), or 0.9% sodium chloride (control group). Sugammadex was administered 5s later following rocuronium. In R group, mast count was higher, and the distribution rate of granules and nuclear changes were different compared with other groups. Distribution rate of granules in groups S16 and S96 were similar to the control group and lower compared with other groups. The amount of mast cells and granule density in groups RS16 and RS96 was lower compared with R group. The amount of mast cells in groups RS16 and RS96 was significantly lower compared with other treatment groups. These results suggest that sugammadex may have an inhibitory effect on mobilization and morphological changes in pancreatic mast cells induced by administration of rocuronium and sugammadex in rats.
Carvone (CVN) is a monocyclic monoterpene found in the essential oils of Mentha spicata var. crispa (Lamiaceae) and Carum carvi L. (Apiaceae) plants and has been reported to have antioxidant, antimicrobial, anticonvulsant, and antitumor activities. The beneficial health properties of CVN have encouraged us to look into its anticancer activity. To the best of our knowledge, reports are not available on the anticancer activity of CVN in cultured primary rat neuron and N2a neuroblastoma (NB) cells. Therefore, the present study is an attempt toward exploring the potential anticancer activity of CVN, if any, in cultured primary rat neuron and N2a NB cells. Our results indicated that CVN (only at 25 mg/L) treatment led to an increase in the total antioxidant capacity levels in cultured primary rat neuron cells compared with control cells. Also, CVN (at concentrations higher than 100 mg/L) treatment led to an increase in the total oxidative stress levels in both cell types. The mean values of the total scores of cells showing DNA damage (for comet assay) were not found to be significantly different from the control values in both cells (p > 0.05). On the other hand, after 24 h treatment with CVN, 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay showed that CVN application significantly reduced the cell viability rates in both cell types at concentrations higher than 100 mg/L. Summarizing, our data suggest that CVN represents little potential for promising anticancer agent to improve brain tumors therapy.
Single-walled carbon nanotubes (SWCNTs) have extensive potential industrial applications due to their unique physical and chemical properties; yet this also increases the chance of human and environment exposure to SWCNTs. Due to the current lack of hazardous effect information on SWNCTs, a standardized genotoxicity battery test was conducted to clarify the genetic toxicity potential of SWCNTs (diameter: 1–1.2 nm, length: ~20 μm) according to Organization for Economic Cooperation and Development test guidelines 471 (bacterial reverse mutation test), 473 (in vitro chromosome aberration test), and 474 (in vivo micronuclei test) with a good laboratory practice system. The test results showed that the SWCNTs did not induce significant bacterial reverse mutations at 31.3–500 μg/plate in Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537 or in Escherichia coli strain WP2uvrA, with and without a metabolic activation system. Furthermore, the in vitro chromosome aberration test showed no significant increase in structural or numerical chromosome aberration frequencies at SWCNT dose levels of 12.5–50 μg/ml in the presence and absence of metabolic activation. However, dose-dependent cell growth inhibition was found at all the SWCNT dose levels and statistically significant cytotoxic effects observed at certain concentrations in the presence and absence of metabolic activation. Finally, the SWCNTs did not evoke significant in vivo micronuclei frequencies in the polychromatic erythrocytes of an imprinting control region mice at 25–100 mg/kg. Thus, according to the results of the present study, the SWCNTs were not found to have a genotoxic effect on the in vitro and in vivo test systems.
The study investigated the toxic effects of diesel and biodiesel derived from opium poppy (Papaver somniferum L.) oil seeds on the trace and major elements in kidney, lung, liver, and serum of rats. By the end of 21 days, trace and major element concentrations in kidney, lung, and liver tissues and the serum were measured using inductively coupled plasma–optical emission spectroscopy. We observed that trace and major element levels in kidney, lung, and liver tissues and the serum changed. Especially, important differences were detected in trace and major element concentrations in kidney and lung tissues. In kidney tissue, the concentration differences of calcium, sodium, and zinc (Zn) were found between diesel and biodiesel groups. In lung tissue, the concentration differences of cadmium, lithium, magnesium, manganese, and Zn were found between diesel and biodiesel groups. Among the significant findings, Zn concentration in serum and liver tissue of diesel and biodiesel were different from control (p < 0.05). However, the metal levels of biodiesel group were similar to control group. Due to lesser toxicity of biodiesel, it could be considered as an alternate fuel.
Benzo[a]pyrene (BaP) is a prototype for studying carcinogenesis of polycyclic aromatic hydrocarbons (PAHs). We have long been interested in studying the phototoxicity of PAHs. In this study, we determined that metabolism of BaP by human skin HaCaT keratinocytes resulted in six identified phase I metabolites, for example, BaP trans-7,8-dihydrodiol (BaP t-7,8-diol), BaP t-4,5-diol, BaP t-9,10-diol, 3-hydroxybenzo[a]pyrene (3-OH-BaP), BaP (7,10/8,9)tetrol, and BaP (7/8,9,10)tetrol. The photocytotoxicity of BaP, 3-OH-BaP, BaP t-7,8-diol, BaP trans-7,8-diol-anti-9,10-epoxide (BPDE), and BaP (7,10/8,9)tetrol in the HaCaT keratinocytes was examined. When irradiated with 1.0 J/cm2 UVA light, these compounds when tested at doses of 0.1, 0.2, and 0.5 μM, all induced photocytotoxicity in a dose-dependent manner. When photoirradiation was conducted in the presence of a lipid (methyl linoleate), BaP metabolites, BPDE, and three related PAHs, pyrene, 7,8,9,10-tetrahydro-BaP trans-7,8-diol, and 7,8,9,10-tetrahydro-BaP trans-9,10-diol, all induced lipid peroxidation. The formation of lipid peroxides by BaP t-7,8-diol was inhibited by NaN3 and enhanced by deuterated methanol, which suggests that singlet oxygen may be involved in the generation of lipid peroxides. The formation of lipid hydroperoxides was partially inhibited by superoxide dismutase (SOD). Electron spin resonance spin trapping experiments indicated that both singlet oxygen and superoxide radical anion were generated from UVA photoirradiation of BPDE in a light dose responding manner.
In this study, lead (Pb), cadmium (Cd) and nickel (Ni) were determined in soil, water, vegetable and fruit samples taken from around oil refinery region in Batman, Turkey. Digestion procedures for samples were optimized and all optimum parameters were used both in digestion and in determination steps. In order to determine Pb and Cd, slotted tube atom trap (STAT) was used to increase the sensitivity in atomic absorption spectrophotometry. Preconcentration procedure under the optimum conditions was applied to water, vegetable and fruit samples to determine Pb, Cd and Ni in trace levels. In soil samples, concentrations of analytes were found in the range of 4.0 ± 0.2–12,000 ± 60 mg/kg for Pb, 0.15 ± 0.01–3.0 ± 0.1 mg/kg for Cd and 21 ± 1–65 ± 3.4 mg/kg for Ni. In all water samples, concentration of Ni was expressed as nanogram per milliliter (ng/mL) and found to be higher than Pb and Cd levels. It was observed that Pb, Cd and Ni concentrations varied from both plant to plant and in same plants at different experimental sites. Pb concentrations in vegetable and fruit samples interested varied between 20 ± 2 and 160 ± 12 ng/g, and the highest level of Pb was found to be in green pepper taken from 1000 m away from refinery.
In the present study, the beneficial effect of hesperidin (HP), a citrus flavonoid, on cisplatin (CP)-induced neurotoxicity was investigated. A total of 28 rats were equally divided into four groups; the first group was kept as control. In the second and third groups, CP and HP were given at the doses of 7 and 50 mg/kg/day, respectively. In the fourth group, CP and HP were given together at the same doses. The results indicated that although CP caused significant induction of lipid peroxidations and reduction in the antioxidant defense system potency in the brain and sciatic nerve, HP prevented these effects of CP. Besides, CP led to histopathological damage, mainly apoptosis, as well as electromyographical (EMG) changes in sciatic nerve. On the other hand, HP treatment reversed histopathological and EMG effects of CP. In conclusion, CP had severe dose-limiting neurotoxic effects and these effects of CP can be prevented by HP treatment. Thus, it appears that coadministration of HP with CP may be a useful approach to attenuate the negative effects of CP on the nervous system.
The aim of this study was to determine oxidative stress status as well as ferrous (Fe) and Copper (Cu) levels in blood, neurocognitive impairment, and clinical markers in iron–steel workers. A comparative cross-sectional analysis was performed in 50 iron–steel workers who have been in contact with Fe and Cu in comparison with a control group containing 50 healthy subjects in the same age group and sex. Blood levels of lipid peroxidation, total antioxidant capacity, Fe, and Cu along with neurocognitive impairment were measured in workers and controls. Clinical examination was accomplished to record any abnormal sign or symptoms. Comparing with controls, the workers showed higher blood levels of lipid peroxidation and Cu and also a lower total antioxidant capacity. There was a positive correlation between work history and interstitial lung disease that strengths the presumption to progress to chronic obstructive lung disease in future. The results indicate that exposure to a combination of Fe and Cu in iron–steel workers induces oxidative stress. Especially, in the present case, toxic effect of Cu has been more than positive effects of Fe, but the combined exposure resulted in no such critical toxicity.
Cisplatin (CP) is a widely used anticancer drug; however, it has several side effects such as nephrotoxicity. Ginger, the rhizome of Zingiber officinale, consumed since ancient times has numerous health benefits. The objective of this work was to evaluate the protective effect of ginger extract (GE) against CP-induced nephrotoxicity. CP group displayed a marked renal failure characterized by a significant increase in serum creatinine and blood urea nitrogen (BUN) levels in addition to severe histopathological and ultrastructural renal alterations. Also, CP group showed an increase in the immunohistochemical expression of Bax proapoptotic protein. In contrast, GE+CP group showed significant decrease in the elevated serum creatinine and BUN levels and an improvement in the histopathological and ultrastructural renal injury induced by CP. The overexpression of Bax proapoptotic protein was significantly decreased in the GE+CP group. Hence, the present results indicated that GE has a protective effect against CP-induced renal damage in rats. Thereby, such findings recommended the usage of GE to prevent and/or decrease the renal damage induced by CP chemotherapeutic treatment.
Propensity of two different silver nanoparticles (Ag-NPs) to bovine hemoglobin (BHb) was investigated by means of spectroscopic methods. We have combined spectrophotometric and calorimetric methods to show that there is no significant interaction between citrate-coated Ag-NPs and BHb at physiological pH and 20°C. However, our previous results show that polyethylene glycol-coated Ag-NPs strongly bind to Hb and effect on the secondary and tertiary structures of BHb. Thus, a suitable surface coating and modification of surface charge would increase the NPs safety and reduce adverse biological responses.
The present investigations were carried out to study the protective potential of four extracts (namely petroleum ether extract (LCR), chloroform extract (LCM), ethyl acetate extract (LCE), and alcoholic extract (LCL)) of Lavandula coronopifolia on oxidative stress-mediated cell death induced by ethanol, a known hepatotoxin in human hapatocellular carcinoma (HepG2) cells. Cells were pretreated with LCR, LCM, LCE, and LCL extracts (10–50 μg/ml) of L. coronopifolia for 24 h and then ethanol was added and incubated further for 24 h. After the exposure, cell viability using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and neutral red uptake assays and morphological changes in HepG2 cells were studied. Pretreatment with various extracts of L. coronpifolia was found to be significantly effective in countering the cytotoxic responses of ethanol. Antioxidant properties of these L. coronopifolia extracts against reactive oxygen species (ROS) generation, lipid peroxidation (LPO), and glutathione (GSH) levels induced by ethanol were investigated. Results show that pretreatment with these extracts for 24 h significantly inhibited ROS generation and LPO induced and increased the GSH levels reduced by ethanol. The data from the study suggests that LCR, LCM, LCE, and LCL extracts of L. coronopifolia showed hepatoprotective activity against ethanol-induced damage in HepG2 cells. However, a comparative study revealed that the LCE extract was found to be the most effective and LCL the least effective. The hepatoprotective effects observed in the study could be associated with the antioxidant properties of these extracts of L. coronopifolia.
This study was carried out to investigate the genotoxic effect of boron (B) on maize using randomly amplified polymorphic DNA (RAPD) method. Experimental design was conducted under 0, 5, 10, 25, 50, 100, 125, and 150 ppm B exposures, and physiological changes have revealed a sharp decrease in root growth rates from 28% to 85%, starting from 25 ppm to 150 ppm, respectively. RAPD-polymerase chain reaction (PCR) analysis shows that DNA alterations are clearly observed from beginning to 100 ppm. B-induced inhibition in root growth had a positive correlation with DNA alterations. Total soluble protein, root and stem lengths, and B content analysis in root and leaves encourage these results as a consequence. These preliminary findings reveal that B causes chromosomal aberration and genotoxic effects on maize. Meanwhile, usage of RAPD-PCR technique is a suitable biomarker to detect genotoxic effect of B on maize and other crops for the future.
<abstract>
Aim of the study:Traditionally herbal formulations have been used effectively for
the management of disorders that are now being accepted worldwide.
Saraca asoca bark extract (SAE) finds use in traditional
herbal medicine. In the present study, SAE were studied for their antioxidant,
antimutagenic, and antigenotoxic properties.
Methods:SAE were evaluated for antimutagenic property in
Salmonella strains (TA97a, TA98, TA100, and TA102), in the
presence and absence of metabolic activation (S9). The SAE was also studied for
antigenotoxic property against cyclophosphamide (CP) in Swiss albino male mice
in vivo. The extract was analyzed using high-performance
liquid chromatography (HPLC).
Results: The study reveals antimutagenic property of the bark extract in
Salmonella strains in the presence and absence of metabolic
activation (S9). The study reports antigenotoxic property of the bark extract
against CP in vivo. Thiobarbituric acid reactive species assay
on the bark extract revealed antioxidant property. HPLC revealed the presence of
two peaks corresponding to gallic acid and (-)-epicatechin, respectively.
Conclusion: The study clearly reveals the antimutagenic and antigenotoxic
properties of SAE.
</abstract>
Penile fracture (PF) is known as a traumatic rupture of the tunica albuginea of corpus cavernosum. In this study, we aimed to investigate the healing influence of topical extra virgin olive oil (EVOO) on PF through evaluating levels of some oxidative stress biomarkers for the first time. Histopathological evaluation was also realized. A total of 18 male Sprague-Dawley albino rats were divided into three groups of six rats each as control group, in PF (alone) group, and PF + EVOO group. Experimental PF was formed via incising from the proximal dorsal side of the penis in the rats of all groups except control. While in PF (alone) group, fracture was formed and the incision was primarily closed, in PF + EVOO group in addition to foregoing processes, EVOO was also administrated topically twice a day for 3 weeks. At the end of the experiment, all rats were killed and penectomy was carried out. While malondialdehyde, myeloperoxidase, lipid hyroperoxide, and total oxidant status significantly (p < 0.05) increased, reduced glutathione and total free sulfhydryl groups markedly (p < 0.05) decreased in PF (alone) group when compared with PF + EVOO group. Levels of these parameters were reversed to nearly normal values by topical EVOO application. Protection by EVOO is further substantiated via the improved histological findings in PF + EVOO group as against degenerative changes in the rats of PF (alone) group. Our data revealed that EVOO has protective effect in penile cavernosal tissue through probably its antioxidant, free radical defusing, anti-inflammatory, and antimicrobial effects.
The aim of this study is to report ophthalmic findings of acute mercury poisoning in 48 adults referred to emergency department. Full ophthalmologic examination including the best corrected visual acuity, external eye examination, reaction to light, a slit-lamp examination, funduscopy, intraocular pressure measurements, and visual field (VF) and color vision (CV) tests were performed at the presentation and repeated after 6 months. The parametric values of VF test, the mean deviation (MD), and pattern standard deviation (PSD) were recorded in order to compare patients and the 30 healthy controls. The mean parameter of color confusion index in patients was found to be statistically different than controls (p < 0.01). The MD and PSD in patients were different from controls statistically significant (p < 0.01 and p < 0.01, respectively). There was no correlation between the ocular findings and the urine and blood mercury levels. Methyl mercury, held in the school laboratory for experimental purpose, may be a source of poisoning. In this case series, we showed that acute exposure to mercury had hazardous effect on the visual system, especially CV and VF. We propose that emphasizing the public education on the potential hazards of mercury is crucial for preventive community health.
Endothelial adhesion plays an important role in the process of atherosclerosis, which is regulated by endothelial adhesion molecules and chemoattractant molecules. In some areas of China, citreoviridin (CIT) is considered a risk factor for the development of atherosclerosis. Here, we investigated the role of CIT in adhesion of human umbilical vein endothelial cells (HUVECs) together with the stimulation of tumor necrosis factor-α (TNF-α). Adhesion of HUVECs to monocytes was analyzed by coculture experiments using U937 cells labeled with 2,7-bis(2-carboxyethyl)-5(6)-carboxyfluorescein acetoxymethylester. The expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin was determined by Western blot and enzyme-linked immunosorbent assay (ELISA). The expression of monocyte chemoattractant protein-1 (MCP-1) was measured by reverse transcription polymerase chain reaction and ELISA. The activation of nuclear factor-B (NF-B) was assessed by Western blot and immunofluorescence staining. CIT markedly increased TNF-α-induced HUVECs adhesion to monocytes and the expression levels of ICAM-1, VCAM-1, E-selectin, and MCP-1. TNF-α-induced nuclear translocation of NF-B in HUVECs was significantly elevated by CIT. Our study demonstrates that CIT upregulates TNF-α-induced endothelial adhesion via increasing activation of NF-B, which results in the expression of ICAM-1, VCAM-1, E-selectin, and MCP-1. CIT plays a pivotal role in the process of endothelial cell adhesion and may thereby play an important role in the improvement of atherosclerosis in areas of China that have a high prevalence of CIT contamination and atherosclerosis.
This investigation was undertaken to compare five different in vitro cytotoxicity assays for their power in revealing vanadium-mediated toxicity in Chinese hamster ovary (CHO)-K1 cells. The cells were exposed to sodium metavanadate (NaVO3) in the range of 10–1000 µM for 24 h and thereafter the cytotoxic effects of NaVO3 were measured by colorimetric in vitro assays: the neutral red (NR) test, the 2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxyanilide inner salt (XTT) assay, the resazurin assay, the sulforhodamine B (SR-B) assay, and by microscopic assessment of cell viability using the trypan blue (TB) staining method. Among the assays used, the NR test was the most sensitive, since it revealed metavanadate cytotoxicity at the lowest NaVO3 dose (=50 µM). Also, NaVO3 cytotoxicity expressed as inhibitory concentration (IC) showed the lowest values for the NR test. Three other tests XTT, resazurin, and SR-B assays showed intermediate sensitivity revealing the cytotoxicity of NaVO3 at 100 µM. The corresponding IC10 and IC50 values calculated for the XTT, resazurin, and SR-B tests were similar. The TB staining method was the least sensitive, since it recorded metavanadate cytotoxicity at the highest NaVO3 concentration tested (=600 µM). Based on the cytotoxicity end points measured with the above assays, it can be concluded that lysosomal/Golgi apparatus damage (measured by NR assay) may be the primary effect of NaVO3 on CHO-K1 cells. The disintegration of mitochondria (assessed with the XTT and resazurin assays) probably follows lysosomal impairment. Plasma membrane permeability (staining with TB) occurs at a late stage of NaVO3-induced cytotoxicity on CHO-K1 cells. The results obtained in this research work show that the NR test can be recommended as a very sensitive assay for the assessment of NaVO3 cytotoxicity in the CHO-K1 cell culture model. Considering the convenience of assay performance along with adequate sensitivity, the XTT and resazurin assays can also be advocated for NaVO3 cytotoxicity assessment.
In liver, the major site of iron storage, iron overload is associated with oxidative damage of protein, lipid, and DNA and causes protein oxidation, lipid peroxidation, and rupture of hepatocytes, leading to cell death. Serum ferritin and liver iron content are the main forecasters of moderate to severe iron overload in the liver. The sequels of excess iron deposition in the liver are fibrosis and enhanced levels of serum enzymes and bilirubin markers. Emblica officinalis (EO) fruit extract was found efficient in lessening intraperitoneally injected iron dextran-induced liver toxicity in Swiss albino mice. Mice administered with different doses of 70% methanol extract of EO (50, 100, and 200 mg kg-1 body weight) showed significant decrease in liver iron, serum ferritin, and serum enzyme levels, along with the decrease in lipid peroxidation, protein oxidation, and collagen content. The activity was further supported by its considerable iron chelation with half-maximal inhibitory concentration of 70.24 ± 2.74 μg ml-1 and the protection on ferrous ion-mediated DNA breakdown with 50% protection ([P]50) of 1.04 ± 0.01 μg ml-1. Simultaneously, the extract effectively induced the antioxidant enzyme levels and also exhibited the potential activity of reductive release of ferritin iron. These findings suggest that the EO extract may be used as a potent drug for the treatment of pathological sequences arisen in the iron overload-induced liver damage.
Contamination of soil and water bodies with spent engine oil and petroleum products is a serious ecological problem, primarily in the automobile workshops and garages. This has potential short and chronic adverse health risks. Information is currently scarce on the potential mutagenicity and genotoxicity of such wastes. In this study, the potential mutagenic and genotoxic effects of simulated leachate from automobile workshop soil in Sagamu, Ogun state, Nigeria, were investigated. The assays utilized were bone marrow micronucleus (MN) and chromosome aberration (CA), sperm morphology and sperm count in mice. The physicochemical analysis of the leachate was also carried out. Experiments were carried out at concentrations of 1, 5, 10, 25, 50, 75 and 100% (volume per volume; leachate:distilled water) of the leachate sample. MN analysis showed a concentration-dependent induction of micronucleated polychromatic erythrocytes across the treatment groups. In the CA test, there was concentration-dependent significant reduction in mitotic index and induction of different types of CAs. Assessment of sperm shape showed a significant increase in sperm abnormalities with significant decrease in mean sperm count in treated groups. Heavy metals analyzed in the tested sample are believed to contribute significantly to the observed genetic damage. This indicates that automobile workshop soil-simulated leachate contains potential genotoxic agents and constitutes a genetic risk in exposed human population.
This study aims to evaluate the protective effects of -3 fatty acids (FAs) on doxorubicin (DOX)-induced hepatotoxicity and nephrotoxicity in rats. A total of 24 adult male Sprague Dawley rats were divided into three groups. Control group was given only saline by intragastric gavage. DOX group received DOX at the dose of 30 mg/kg intraperitoneally on day 28. DOX--3 FA group was given as -3 FAs at the dose of 400 mg/kg daily by intragastric gavage for 30 days and received DOX at the dose of 30 mg/kg intraperitoneally on day 28. At the end of the 30-day experimental period, the serum, liver and kidney tissue specimens were taken from the animals by giving a general anesthesia. Glutathione (GSH) and malondialdehyde (MDA) levels in serum and GSH and MDA levels and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in liver and kidney tissues were measured spectrophotometrically. In our study, a significant increase in MDA levels was observed in rats when given a dose of DOX and a significant decrease in the levels of GSH, SOD and GSH-Px activities in serum, liver and kidney tissues was determined when compared with control group. In addition, a significant decrease in MDA levels was observed in rats when a dose of -3 FAs was given with DOX and a significant increase was determined in the levels of GSH, SOD and GSH-Px activities in serum, liver and kidney tissues, when compared with DOX group. We concluded that -3 FA had favorable effects in rat liver and kidney tissues by preventing oxidative damage.
This trial was conducted to investigate the effect of chest physiotherapy in different positions on the heart and the respiratory system after coronary artery bypass surgery. Patients are divided into two groups of 30 patients each in the study. To the patients in the first group (30 patients), percussion–vibration was performed in the 45° supine position, while slightly laterally lying and endotracheal aspiration was performed in the supine position. To the patients in the second group (30 patients), percussion–vibration was performed in the 0° supine position, while slightly laterally lying and endotracheal aspiration was performed in the supine position. The procedures are repeated two times for all patients and their means were taken. The pre- and postapplication values of patients were measured from central venous and arterial catheters and the values of patient monitors were recorded. Comparison of the two groups in terms of respiratory values did not reveal a significant difference, but chest physiotherapy with the head of the bed at 0° was determined to improve cardiac functions. Evaluation of the groups in terms of pre- and postphysiotherapy applications showed a significant increase in mixed venous oxygen saturation in both groups. Chest physiotherapy with the head of the bed elevated to 45° may be recommended in patients who carry a risk of pulmonary complications and who are candidates for chest physiotherapy at an early stage.
Diclofenac (DCF) is among the most commonly used nonsteroidal anti-inflammatory drugs worldwide for the treatment of various conditions in postpubertal women. However, very limited information is available regarding its safety during pregnancy and teratogenecity. The present study was designed to elucidate the effects of DCF on the developing rat embryos during the major organogenesis period and investigate the critical role of apoptosis in bringing about these congenital anomalies. Embryos were exposed in vitro to various concentrations of DCF, that is, 0, 3.75, 7.5 and 15 µg/ml for 24 h, respectively, and examined for the growth and differentiation at the end of the culture period for the presence of any specific malformations. Growth and developmental parameters such as weight of embryos, crown–rump length and number of somites were found to be lower in the embryos exposed to high concentrations of DCF (7.5 and 15.0 μg/ml) when compared with the untreated control. However, no significant difference in growth parameters was found between embryos exposed to 3.75 µg/ml and the control group. In parallel to this, flow cytometric analysis and DNA quantitation of cultured rat embryos were performed to verify the involvement of apoptosis in mediating DCF-induced teratogenesis. A concentration-dependent increase in apoptosis in embryos suggests a possible engagement of apoptosis in the role of DCF as a teratogenic agent. A detailed analysis of the actual effect of DCF on cellular apoptotic machinery necessitates further evaluation.
Background: Corrosive esophageal injury causes serious clinical problems. We aimed to create a new experimental esophageal burn model using a single catheter without a surgical procedure. Materials and methods: We conducted the study with two groups of 12 male rats that fasted for 12 h before application. A modified Foley balloon catheter was inserted into the esophageal lumen. The control group was given 0.9% sodium chloride, while the experimental group was given 37.5% sodium hydroxide with the other part of the catheter. After 60s, esophagus was washed with distilled water. The killed rats were examined using histopathological methods after 28 days. Results: In comparison with the histopathological changes experienced by the study groups, the control groups were observed to have no pathological changes. Basal cell degeneration, dermal edema, and a slight increase in the keratin layer and collagen density of submucosa due to stenosis were all observed in the group subjected to esophageal corrosion. Conclusion: A new burn model can thus, we believe, be created without the involvement of invasive laparoscopic surgery and general anesthesia. The burn in our experiment was formed in both the distal and proximal esophagus, as in other models; it can also be formed optionally in the entire esophagus.
Now-a-days, there is a big need to reduce genotoxic effects of mutagenic and carcinogenic agents in environment, which are increased by the technological development. Lichens produce a wide variety of unique metabolites due to being in various extreme areas and being symbiotic organisms of fungi and algae. Therefore, this study was planned to search new sources having antimutagenic activity by researching two different lichen species and to determine whether their usage is safe. With this respect, the mutagenic and antimutagenic properties of methanol extracts of the lichens were determined by the bacterial reverse mutation and sister chromatid exchange assays. Furthermore, the malondialdehyde level, superoxide dismutase, glutathione and glutathione peroxidase activities against aflatoxin B1 were determined for understanding the ways in which the lichens showed their genotoxic properties.
The present study was performed to investigate the effect of Urtica dioica (UD) on liver regeneration after partial hepatectomy (PH) in rats. A total of 24 male Sprague Dawley rats were divided into three groups: sham-operated, PH and PH + UD; each group contains eight animals. The rats in UD-treated groups were given UD oils (2 ml/kg/day) once a day orally for 7 days starting 3 days prior to hepatectomy operation. At day 7 after resection, liver samples were collected. The levels of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) were estimated in liver homogenates. Moreover, histopathological examination, mitotic index (MI), proliferating cell nuclear antigen labeling, proliferation index (PI), transferase-mediated deoxyuridine triphosphate nick end-labeling assay, apoptotic index (AI) were evaluated at day 7 after hepatectomy. As a result, UD significantly increased MI and PI, significantly decreased AI and also attenuated hepatic vacuolar degeneration and sinusoidal congestion in PH rats. UD treatment significantly decreased the elevated tissue MDA level and increased the reduced SOD activity and GSH level in the tissues. These results suggest that UD pretreatment was beneficial for rat liver regeneration after partial hepatectomy.
Nowadays, food dyes obtained from herbal, animal, microbial and mineral sources are widely used as food additives. In this study, the toxic effects of three different natural food dyes (carmine, turmeric and annatto) on 72 ± 4 h larvae of Oregon-R wild type of Drosophila melanogaster were investigated. For this purpose, four different application doses (50, 75, 100, 125 mg mL-1) were chosen by means of preliminary studies. It was determined that larval mortality increased with increasing concentration in the application groups and the toxicity order was carmine > turmeric > annatto. It was observed that the survival rate was highest in the control with 98% and lowest in 125 mg mL-1 carmine with 16%. In addition, the average lifespan of the adult individuals obtained from third instar larvae was also studied. While the average lifespan was 40.88 ± 1.44 days in the control group, these values were 10.81 ± 0.55–23.90 ± 1.27 days in the carmine group, 15.00 ± 0.80–22.42 ± 1.43 days in the turmeric group and 10.33 ± 1.03–35.68 ± 1.54 days in the annatto group, respectively. According to the obtained results, when both the developmental period from larvae into adults and the lifespan of the developing adults were compared with the control group, the food dyes were found to be toxic and the toxicity order of carmine > turmeric > annatto was identified.
Introduction: Acute inhalational exposure leads to rapidly progressive acute respiratory distress syndrome (ARDS). This report is the first one to present a patient with ARDS in relation to long-standing exposure to a high-concentration mixture of ethenone and crotonaldehyde. Case report: A male worker in a chemical plant was accidentally exposed to the mixture of high-concentrated ethenone and crotonaldehyde for 5 min in an open space and worked continuously in the polluted area for approximately 12 h. On admission, he was conscious with the following vital parameters: blood pressure, 151/91 mmHg; pulse rate, 107 beats/min; respiratory rate, 30 breaths/min; temperature, 37.6°C; oxygen saturation, 92% supported by mask saturation 10 L/min; arterial blood gases showed P/F oxygen ratio of less than 200. Physical examination disclosed decreased bilateral vesicular sounds. A chest computed tomography revealed bilateral nonsegmental ground-glass opacities. The patient was mechanically ventilated and treated with corticosteroid. The patient was discharged without any symptoms. Conclusion: Exposure to mixtures of ethenone and crotonaldehyde can cause severe pulmonary injury leading to delayed ARDS.
The aim of the present study was to determine the effects of extremely low-frequency magnetic field (ELF-MF) on accumulation of manganese (Mn) in the kidney, liver and brain of rats. A total of 40 rats were randomly divided into eight groups. Four control groups received 0, 3.75, 15 and 60 mg Mn per kg body weight orally every 2 days for 45 days, respectively. The remaining four groups received same concentrations of Mn and were also exposed to ELF-MF (1.5 mT; 50 Hz) for 4 h for 5 days a week during 45 days. Following the last exposure, kidney, liver and brain were taken from all rats and they were analyzed for Mn accumulation levels using an inductively coupled plasma-optical emission spectrometer. In result of the current study, we observed that Mn levels in brain, kidney and liver were higher in Mn groups than in control groups. Mn levels in brain, kidney and liver were also higher in Mn plus ELF-MF groups than in Mn groups. In conclusion, result of the current study showed that the ELF-MF induced manganese accumulation in kidney, liver and brain of rats.
The major objective of the present investigation was to assess the genotoxic effects of mercuric chloride (HgCl2), an inorganic mercury (Hg), in rats (Rattus norvegicus) using two different genetic endpoints, namely, chromosomal aberration (CA) and comet assays following both short-term (acute) and long-term (chronic) exposures. The study showed that the acute exposures to HgCl2 at 2 and 5 mg/kg body weight (b.w.) induced nonsignificant effects. HgCl2 at 10 and 12 mg/kg b.w. was significantly toxic and is exhibited by the induction of different types of CAs like chromatid breaks, chromosomal breaks, clumps and damaged cells and types of comets. HgCl2 at 15 mg/kg b.w. was found to be highly toxic, as mitostatic condition of cells were observed in CA assay. Chronic exposure to the lowest dose (2 mg/kg b.w.) of HgCl2 for 15 consecutive days produced a significant genotoxicity. Although Hg was found to induce both DNA strand breakage and chromosomal breaks in a dose-dependent manner, the results of the present investigation showed that the combination of comet and CA assays provided a better choice for assessing the genotoxicity of inorganicHg.
Objective: To establish if serum levels of interleukin-10 (IL-10) in subjects exposed to benzene are connected with age, working years, and employment age. Methods: We evaluated serum levels of IL-10 in 51 employees working in oil refinery (group A) and in 16 office workers who resided in the same area (group B). Results: There was no statistically significant difference between serum concentrations of IL-10 in groups A and B. There was a statistically significant dependent relationship in group A between age, working years, and serum concentration of IL-10. There was a statistically significant and positive dependent relationship in group A between serum concentration of IL-10 and employment age. Conclusions: The role played by IL-10 in benzene immune suppression may be relevant and attention should be directed toward assessment of age, working years, and employment age in benzene-exposed populations.
In this study, the subject of heavy metal concentration in soil, rock, sediment, surface water and groundwater, which can be caused by natural or man-posed pollution, was analyzed in the industrial park of Rasht. These concentrations were compared with the standard range of environmental data. Heavy metals are important environmental pollutants that can cause health hazards to humans, plants and microorganisms by entering food chain. This study aimed to investigate the absorption of lead by the leaves of sycamore tree species in the industrial park of Rasht. For this purpose, a sample of 32 sycamore tree species were randomly selected at a specified time, and the concentration of lead were measured using an atomic absorption device. Results showed that the amount of lead absorption by sycamore leaves is remarkable. The highest amount of lead absorption by sycamore leaves was detected at station 1 (Khazar Steel) and the lowest amount at station 2 (control station).
Launaea procumbens methanol extract (LPME) was evaluated against carbon tetrachloride (CCl4)-induced pancreatic oxidative damage and hyperglycemia in rats. Various doses of the extract were administered to rats after 48 h of CCl4 treatment (3 ml/kg bodyweight (bw); intraperitoneally, 20% CCl4/olive oil) twice a week for 4 weeks. Coadministration of various concentrations of LPME (100, 150 and 200 mg/kg) ameliorated the toxicity of CCl4 and reversed the serum level of enzymes (amylase and lipase), glucose and hormone (insulin). The extract was able to reduce thiobarbituric acid reactive substance but increased the glutathione contents in pancreatic tissue. Depletion of antioxidant enzyme activities (catalase, peroxidase, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase and glutathione-S-reductase) and DNA damages induced with CCl4 were restored by LPME supplement. It is suggested that LPME effectively protects the liver against the CCl4-induced oxidative damage in rats, possibly through antioxidant and/or free radical scavenging effects of flavonoids and phenolic compounds in the extract.
The aim of the study was to assess the effects of exposure to low doses of lead dissolved in drinking water (average daily dose of 2.2 mg kg-1 day-1) on selected carbohydrate metabolism parameters in 20 wistar rats. Animals were divided into two groups – control (C) (group drinking clear water) and experimental group (Pb; group exposed to low doses of lead acetate in a concentration of 100 μmol l-1 of drinking water). In this study, we studied the biochemical parameters (glucose, haemoglobin (Hb), glycated haemoglobin (HbA1c), lactate dehydrogenase (LDH) and amylase (AMS)) in rat blood. Glucose and Hb concentration and AMS activity decreased, LDH activity increased but HbA1c concentration levels did not change in rats exposed to lead. Our results well documented that lifetime exposure to lead affected carbohydrate metabolism of rats. Some parameters like concentration of Hb as well as activities of AMS and LDH are useful markers of intoxication of rats with lead. For the evaluation of results (e.g. AMS), not only the data at the end of the experiment should be taken into account but also the entire duration of trials (i.e. more time steps) that makes results more objective should be considered.
The study determined the maximum intraperitoneal (ip) scopolamine dose inducing memory impairment in rats (2 mg/kg) compared to 0.5 or 1 mg/kg dose. The effect reflected by significant increase from normal in the latency time required for rats to find the hidden platform in water maze task and acetylcholinesterase (AChE) activities in cortex, hippocampus and striatum. The dose-related histopathological effect via the hemorrhage, vacuolation and gliosis in cortex and hippocampus is assessed. Then the study investigated the potency of Panax ginseng root extract on scopolamine cognitive dysfunction rat model compared to memantine hydrochloride as reference Food and Drug Administration approved. Ginseng extract was administered at dose 100 or 200 mg/kg/day and memantine at 20 mg/kg/day orally for 2 weeks. All treatments showed improvement in the water maze task, however, ginseng (200 mg/kg) group acquired the advantage without statistical difference control. Scopolamine (2 mg/kg ip) group showed significant increase in AChE reactivity and glutamate level and reduced monoamines (norepinephrine, dopamine and serotonin) and -aminobutyric acid contents in cortex, hippocampus and striatum. Ginseng extract in a dose-dependent manner appears effective as memantine and can improve memory impairment through the retrieved homeostasis via neurotransmitter levels and AChE activities in rat brain areas with partial effect on the histological feature of the brain tissue.
Benzo(a)pyrene (B(a)P), which is commonly used as an indicator species for polycyclic aromatic hydrocarbon (PAH) contamination, has a large number of hazardous consequences on human health. In the presence of the enzyme cytochrome-P-450 1A1 (CYP1A1), it undergoes metabolic activation to form reactive intermediates that are capable of inducing mutagenic, cytotoxic, teratogenic and carcinogenic effects in various species and tissues. Research within the last few years has shown that flavonoids exhibit chemopreventive effect against these toxins. In the present study, the protective effect of silymarin (a flavonoid) against B(a)P-induced toxicity was monitored in Wistar rats by evaluating the levels of hepatic phase I (CYP1A1), phase II enzymes (glutathione-S-transferase, epoxide hydroxylases, uridinediphosphate glucuronosyltransferases, NAD(P)H: quinone oxidoreductase 1, sulfotransferases), cellular antioxidant enzyme heme oxygenase and total glutathione. The results reveal that silymarin possesses substantial protective effect against B(a)P-induced damages by inhibiting phase I detoxification enzyme CYP1A1 and modulating phase II conjugating enzymes, which were confirmed by histopathological analysis. Overall, the inhibition of CYP1A1 and the modulation of phase II enzymes may provide, in part, the molecular basis for the effect of silymarin against B(a)P.
Pesticides and other chemicals at environmental concentrations often have detrimental effects. Many aquatic species are particularly threatened because of their susceptibility and also because water environment are often polluted. This study preliminarily evaluated the toxicity effect of dichlorvos (DDVP) on loach (Misgurnus anguillicaudatus) using the methods of micronucleus (MN) test, hepatase activity and comet assay. The tested results showed that indeed very little DDVP had strong toxicity effect on loach and its 50% lethal concentration (LC50) at 24 h, 48 h and 96 h was 8.38 μg l-1, 7.168 μg l-1 and 6.411 μg l-1, respectively; The glutamic-pyruvic transaminase (GPT) and glutamic–oxalacetic transaminase (GOT) activity of loach liver decreased; meanwhile, the GPT and GOT activity of loach serum, the MN rate () and three comet parameters of tested fish increased with the increase in the treatment concentration and treatment time of DDVP, and there was significant difference between control group and each treatment group (p < 0.05). These results suggested that DDVP residues might become toxic chemical contaminant in environment and would threaten aquatic and other organisms.
Important heavy metals such as lead and cadmium are part of the pollutants produced by cars and are spread in the urban environment by traffic flow. In order to study the amount of contamination in the trees along the streets and to determine the traffic parameters that affect the lead content in sycamore leaves in Rasht, four stations on the margins of the city streets were selected for this case study in terms of traffic volume (low or high). Traffic parameters including three high-traffic stations considering daily and monthly traffic volumes and one low-traffic station were selected. First, 32 sycamore bases were randomly chosen at the intervals of 10–15 m from the whole range of tree canopy in order to determine the absorption of lead; and then, 20 g of each sample were tested to determine the amount of lead absorption. The results of this study, on the amount of lead absorption by the sycamore tree species at three high-traffic and one control station, showed that Takhti station had the highest amount of lead absorption (37.19 ppm) compared with other three stations. Therefore, the sycamore tree species can be an appropriate one for the margins of urban streets.
Lambda-cyhalothrin (LTC) is a synthetic pyrethroid with a broad spectrum of insecticidal and acaricidal activities used to control a wide range of insect pests in a variety of applications. However, there is little known about its adverse effects, in particular those related to its genotoxicity in humans. To elucidate the genotoxicity mechanisms of LTC, the micronuclei (MN) frequencies, the levels of reactive oxygen species (ROS), erythrocyte osmotic fragility, nitrite (NO) formation, protein carbonyl (PCO) levels and malondialdehyde (MDA) production were evaluated for a period of 7, 14 and 21 days. Our results show that exposure rat to LTC (1/10DL50 = 6.23 mg/kg) for a period of 7, 14 and 21 days induced a noticeable genotoxic effect in rat peripheral blood evidenced by a significant increase in the frequency of MN only at day 21 of treatment. Significant differences between the two groups were observed in erythrocyte osmotic fragility. Further, a significant (p < 0.01) increase in ROS contents, NO formation, PCO levels and lipid peroxidation in erythrocytes were observed at different times of treatments, suggesting the implication of oxidative stress in its toxicity. These results confirm the genotoxic and the pro-oxidant effects of LTC in rat peripheral blood.
Diazinon (DZN) is one of the most widely used insecticides in agricultural pest control. Previous studies have shown that DZN may induce hepatotoxicity. Reactive oxygen species and apoptosis pathways are involved in the toxicity of DZN. Crocin, a constituent of saffron, has hepatoprotective effects due to its antioxidant activity. In this study, we examined the effects of subacute DZN exposure and ameliorating effect of crocin on lipid peroxidation and pathological changes in rat liver. Moreover, protein levels of activated and total caspases-3 and -9 and Bax/Bcl-2 ratio were measured. Five groups of rats were used in the experiment. Corn oil (control), DZN (15 mg/kg per day, orally) and crocin (12.5, 25 and 50 mg/kg per day, intraperitoneally in combination with DZN) were given to male Wistar rats (n = 6) for 4 weeks. The level of malondialdehyde (MDA) increased significantly in DZN group compared with the control group (p < 0.05). MDA level decreased significantly in the group that received DZN plus 25 mg crocin (p < 0.001). No gross or histological evidence of treatment-related damage to the liver after oral exposure to DZN was observed. DZN also induced apoptosis through activation of caspases-9 and -3 and increasing Bax/Bcl-2 ratio. Crocin attenuated the activation of caspases and reduced the Bax/Bcl-2 ratio. It is concluded that subacute exposure to DZN induces oxidative stress-mediated apoptosis and crocin may reduce DZN-induced hepatotoxicity.
To understand the genotoxic consequences of chemical agents, random amplification of polymorphic DNA (RAPD) as a useful biomarker to be used as an investigation tool for environmental toxicology. In this study, sodium dodecyl sulfate (SDS) was used as a toxic anionic surfactant, and glutamic acid-based cationic bicatanar surfactant (GS) was used as less toxic cationic amino acid-based surfactant. Experimental results show significant correlations between the RAPD profile changes with root growth, mitotic activity and chromosomal aberration test. The inhibitory rates of root growth at 400 ppm of SDS and GS were 85% and 32%, respectively. Mitotic activity results showed a drastic decrease in SDS exposures, whereas there was no significant decrease in GS treatment. Comparison of the chromosomal aberration test results, rates were indicated at 100, 200 and 400 ppm of SDS and GS; 10, 17, 26 (SDS) and 6, 9, 9 (GS) consequently. Also DNA alterations started at 100 and 200 ppm during SDS and GS exposures, respectively. These preliminary findings encourage the utilization of GS as an environmental friendly surfactant detected by these tools in the investigation of genotoxicity potentials of SDS and GS on maize and the other crops.
In a cross-sectional design, 292 schoolchildren living around a shipyard area, known to be contaminated with lead from shipyard industry, were examined to verify the association between lead exposure and periodontal health. The probing pocket depth (PD), bleeding on probing, plaque and calculus, and the presence of Aggregatibacter actinomycetemcomitans (Aa) in subgingival crevices were recorded. Gingival inflammation was the most common (98%) among children in the area. No significant difference in gingival inflammation was observed between high blood lead (PbB) and low PbB children. The prevalence rate of probing PD of ≥5 mm was 14%. The high PbB group showed more deep pockets at tooth 16 (upper right first permanent molar) and tooth 46 (lower right first permanent molar) than the low PbB group. The odds ratios (ORs) for having probing PD ≥5 mm after adjusting for other factors were 3.63 (95% confidence interval (CI), 1.24–10.61; p = 0.02) for tooth 16 and 3.93 (95% CI, 1.18–13.00; p = 0.02) for tooth 46. The presence of Aa was observed in 17% of the children and it significantly increased in high PbB compared with low PbB children at tooth 46 (OR = 5.53, 95% CI: 1.68–18.15; p = 0.005). This study may suggest no association between lead exposure and gingival inflammation, yet there was the involvement of deeper periodontal tissue in lead-exposed children.
Atherosclerosis is a condition caused by lipid build-up and inflammation in the arteries, so hyperlipidemia is the major reason for atherosclerosis. Testis was found to be negatively affected by hyperlipidemia which leads to its impaired functions. Vitamin E and <sc>l</sc>-carnitine have well-known lipid-lowering and antioxidative activities. Triton WR 1339 is a non-ionic detergent, which induces severe hyperlipidemia by inhibition of lipoprotein lipase. The present study evaluates the protective role of vitamin E and <sc>l</sc>-carnitine on the testis in atherosclerosis and detects the most effective choice for protection against atherosclerosis; vitamin E, <sc>l</sc>-carnitine or a combination of both. A total of 80 albino male rats were divided into eight groups (10 rats for each group): control (G1), triton (G2), <sc>l</sc>-carnitine (G3), triton + <sc>l</sc>-carnitine (G4), vitamin E (G5), triton + vitamin E (G6), <sc>l</sc>-carnitine + vitamin E (G7) and triton + <sc>l</sc>-carnitine + vitamin E (G8). Data showed a significant increase in the levels of total cholesterol (TC), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), 17 beta hydroxysteroid dehydrogenase (17 β HSD), testicular catalase and malondialdehyde (MDA) in G2 when compared with G1, whereas high-density lipoprotein cholesterol (HDL-C), serum testosterone, testicular 17 ketosteroid reductase (17 KSR), total thiol and glutathione-S-transferase (GST) data showed a significant decrease in G2 when compared with G1. Treatment with <sc>l</sc>-carnitine or/and vitamin E helps in improving the adverse effect of triton; also the histological changes confirm this finding. So the present study recommends all people to include <sc>l</sc>-carnitine and vitamin E in their diet to be protected against atherosclerosis.
The aim of this study was to evaluate the effect of tocopherol on pleuritis-induced rats exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Rats were treated with a single TCDD dose of 5 μg/kg body weight (b.w.) and then for 3 weeks they were daily supplemented with tocopherol at a dose of 30 mg/kg b.w. The inflammation was initiated by intrapleural injection of a single dose of 1% carrageenin solution in a volume of 0.15 ml. Changes in biochemical blood parameters were measured three times at the 24th, 72nd and 120th hour of pleuritis and the blood was collected from 20 animals of each group of rats (group with the control inflammation; group treated with TCDD and with control inflammation; group treated with TCDD, supplemented with tocopherol and with the inflammation). The following biochemical parameters were measured: tumor necrosis factor (TNF), interleukin-1 (IL-1), IL-2, IL-4, IL-6, procollagen, telopeptide, fibrinogen, cholesterol, urea, creatinine, aspartate aminotransferase (AspAT) and alanine aminotransferase (AlAT). Daily supplementation of tocopherol caused significant changes in the level of TNF, IL-1, IL-4, IL-6, urea, creatinine, AspAT and AlAT. According to the results of these studies, we suggest that tocopherol supplementation in high doses could act as a protective treatment to improve liver metabolism.
The concentrations of heavy metals (cadmium (Cd), copper (Cu), nickel (Ni), lead (Pb) and zinc (Zn)) were measured in hepatopancreas and muscle of a commercial shrimp (Metapenaeus affinis), in the muscle, liver and gills of two fish species (Thryssa vitrirostris and Johnius belangerii) and in the sediment samples taken from the mouth of the Arvand river, Meleh estuary and Musa estuary in the northeast Persian Gulf. Concentration of heavy metals varied depending on different tissues, species and sampling sites. Liver of fish and hepatopancreas of shrimp exhibited higher metals’ concentration than the other tissues. Generally, in the mouth of the Arvand river, the highest concentration of metals was found in benthic species; while in the mouth of Musa estuary, the highest level of the metals was found in pelagic fish species. Bioaccumulation factors were observed to follow the order: J. belangerii-liver-Cd > T. vitrirostris-liver-Pb > M. affinis-hepatopancreas-Zn > M. affinis-hepatopancreas-Cu > M. affinis- hepatopancreas-Ni. The analysed heavy metals were found in sediment samples at mean concentration in the sediment quality guideline proposed by National Oceanic and Atmospheric Administration (NOAA) and Regional Organization for the Protection of The Marine Environment (ROPME), except for Ni concentration in some cases.
Mentha is a medicinal and aromatic plant belonging to the Lamiaceae family, which is widely used in food, flavor, cosmetic and pharmaceutical industries. Recently, it has been found that the use of Mentha as a pharmaceutical source is based on its phytochemical constituents that have far been identified as tannins, saponins, phenolic acids and flavonoids. This study was designed to evaluate the mutagenic and antimutagenic activities of apigenin 7-O-glucoside (A7G), a flavonoid isolated from Mentha longifolia (L.) Hudson subspecies longifolia (ML). The possible antimutagenic potential of A7G was examined against mutagens ethyl methanesulfonate and acridine in an eukaryotic cell system Saccharomyces cerevisiae and sodium azide in Salmonella typhimurium TA1535 and 9-aminoacridine in S. typhimurium TA1537. According to our findings, any concentrations of the A7G used did not show mutagenic activity but exerted strong antimutagenic activities at tested concentrations. The inhibition rates for the Ames test ranged from 27.2% (S. typhimurium TA1535: 0.4 μM/plate) to 91.1% (S. typhimurium TA1537: 0.2 μM/plate) and for the yeast deletion assay from 4% to 57.7%. This genotoxicological study suggests that a flavonoid from ML owing to antimutagenic properties is of great pharmacological importance and might be beneficial to industries producing food additives, cosmetics and pharmaceuticals products.
This study was conducted to compare the effects of oral toxicity induced by fish oil biodiesel and diesel fuel. Diesel and fish oil biodiesel were administered by oral gavage to rats. For this purpose, 35 rats were divided into five groups. Sunflower oil of 250 mg kg-1 was administered to the rats in the control group by oral gavage. The rats in the D250 and D500 groups were administered by oral gavage 250 mg kg-1 and 500 mg kg-1 of diesel fuel dissolved in equal amounts of sunflower oil, respectively. The rats in the F250 and F500 groups were administered by oral gavage 250 mg kg-1 and 500 mg kg-1 of fish oil biodiesel dissolved in equal amounts of sunflower oil, respectively. At the end of the study, malondialdehyde (MDA) and reduced glutathione (GSH) levels were measured in the whole blood; catalase (CAT) activity level was measured in erythrocytes; and nitrite (NO2) and nitrate (NO3) levels were measured in the serum. It was observed that the whole blood MDA levels of the diesel groups were considerably different from those in the control and fish oil biodiesel groups (p < 0.001). GSH levels in the control group were observed to be considerably different from those in all other groups (p < 0.001). Serum NO3 concentrations in the diesel groups were found to be considerably different from those in the control and biodiesel groups. Serum NO2 concentrations in one of the diesel groups were significantly different from those in the control and biodiesel groups (p < 0.01 and p < 0.05, respectively). The CAT activity of the control group was observed to be different from that in the other groups. According to these results, both fish oil biodiesel and diesel fuel are thought to cause lipid peroxidation. It was observed that fish oil biodiesel does not induce as much oxidative damage as does the diesel fuel. It is suggested that fish oil biodiesel should be preferred as an alternative to the diesel.
Carbonic anhydrase (CA) is a widely distributed enzyme and has a crucial role in the cells, tissues and organs of living organisms. It is found that CA-II is one of the most abundant CA isoenzymes in the gastrointestinal system. It plays an important role in the gastric acid secretion in stomach. In this study, we purified CA-II isoenzyme from sheep stomach with a 615.2 purification fold, 78% purification yield and 5562.02 specific activity. Moreover, the in vitro effects of some commonly used pesticides including chlorpyrifos, cypermethrin, dichlorvos, glyphosate isopropylamine and lambda cyhalomethrin on the enzyme activity were investigated. Of these compounds, glyphosate isopropylamine and dichlorvos showed an inhibition on CA-II esterase activity. They have IC50 values of 0.155 µM and 2.690 µM and Ki values of 0.329 µM and 3.654 µM, respectively. Both glyphosate isopropylamine and dichlorvos inhibited CA-II isoenzyme in a noncompetitive manner.
Botanical insecticides have introduced a new concept in insecticide research. In response to insect attacks, some plants can release volatile compounds that alter insect metabolism and nervous system activity. In the present study, changes in the electrical activity of chemoreceptors and alteration of the fine structure of metathoracic ganglia of desert locust were examined after acute exposure to dimethyl disulfide (DMDS), a sulfur compound released from Allium porrum. Animals were exposed to 1/4 LC50 of DMDS (0.375 μl/L air) and electrophysiological and electron-microscopical studies were carried out. Application of DMDS showed an increase in the activity of deterrent cells present in tarsal chemosensilla of locust. On the other hand, evident degenerative changes in the neurons, neuroglia, neuropile and synaptic vesicles were observed in the metathoracic ganglia of DMDS-treated animals. These findings revealed that pest control using DMDS might be feasible and future work is highly recommended in this respect.
The present study investigated the impact of two doses, 500 mg/kg and 1000 mg/kg, of di(2-ethylhexyl) phthalate (DEHP) and studied the possible therapeutic dose of celery oil seed extract for 6 weeks on some atheroscelerogenic, obesogenic, antioxidant and liver functions in rats. Both doses of DEHP caused over-expression of peroxisome proliferator–activated receptor alpha (PPARα) messenger RNA with significant increase in liver weights, relative liver weights, serum cholesterol (Chol), triglycerides, low-density lipoprotein Chol, liver total lipids, along with an increase in the activities of serum aspartate aminotransferase, alanine aminotransferase, serum endothelin 1 and liver tissue thiobarbituric acid reactive substances (TBARS). Additionally, DEHP administration to rats resulted in significant decrease in final body weights, serum total protein, albumin, liver total protein and serum total nitric oxide. Our study confirmed the role of oral combination of Apium graveolens (celery) oil seed extract at small cumulative doses (50 µl/kg for 6 weeks) with DEHP in ameliorating the toxicological effects of DEHP, which was revealed in reducing the expression of PPARα, lipid profile, with restoring liver functions, vascular oxidative stress and inhibition of TBARS activity.
The effects of different treatments with flavour enhancers monosodium glutamate, monopotassium glutamate, calcium diglutamate, monoammonium glutamate, and magnesium diglutamate on the cytology, DNA content, and interphase nuclear volume (INV) of A. cepa were investigated. Three concentrations of these additives – 20, 40, and 60 ppm – were applied for 6, 12, and 24 h. All the concentrations of these chemicals showed an inhibitory effect on cell division in root tips of A. cepa and caused a decrease in mitotic index values. Additionally, all the treatments changed the frequency of mitotic phases when compared with the control groups. These compounds increased chromosome abnormalities, among them are micronuclei, c-mitosis, anaphase bridges, stickiness, binucleus, laggards, and breaks. The nuclear DNA content and INV decreased when compared with control groups.
The present study was undertaken to determine whether subacute treatment with aqueous extract of carob (Ceratonia siliqua L.) pods (AECPs) protects against ethanol (EtOH)-induced oxidative stress in rat liver. Animals were divided into four groups: control, carob, EtOH and EtOH + carob. Wistar rats were intraperitoneally pretreated with AECP (600 mg/kg body weight (bw)) during 7 days and intoxicated for 6 h by acute oral administration of EtOH (6 g/kg bw) 24 h after the last injection. We found that acute administration of EtOH leads to hepatotoxicity as monitored by the increase in the levels of hepatic marker aspartate aminotransferase and alanine aminotransferase as well as hepatic tissue injury. EtOH also increased the formation of malondialdehyde in the liver, indicating an increase in lipid peroxidation and depletion of antioxidant enzyme activities as superoxide dismutase, catalase and glutathione peroxidase. Subacute carob pretreatment prevented all the alterations induced by EtOH and returned their levels to near normal. Importantly, we showed that acute alcohol increased hepatic and plasmatic hydrogen peroxide and free iron levels. The carob pretreatment reversed EtOH effects to near control levels. These data suggest that carob could have a beneficial effect in inhibiting the oxidative damage induced by acute EtOH administration and that its mode of action may involve an opposite effect on plasma and tissue-free iron accumulation. Indeed, carob can be offered as a food additive to protect against EtOH-induced oxidative damage.
Glucose 6-phosphate dehydrogenase (<sc>d</sc>-glucose 6-phosphate: NADP+ oxidoreductase, EC 1.1.1.49; G6PD) is a key enzyme that is localized in all mammal tissues, especially in cytoplasmic sections and that catalyzes the first step of pentose phosphate metabolic pathway. In this study, G6PD enzyme was purified 1444-fold with a yield of 77% from rainbow trout liver using 2',5'-ADP-sepharose-4B affinity chromatography. Moreover, a purity check of the enzyme was performed with sodium dodecyl sulfate–polyacrylamide gel electrophoresis. Some characteristic features like optimal pH, stable pH, optimal temperature and optimal ionic strength were determined for the purified enzyme. In addition to this, in vitro effects of ions like silver nitrate (Ag+), thallium sulphate (TI+), cobalt (II) nitrate (Co2+) and arsenic (V) oxide (As5+) on enzyme activity were researched. Half-maximal inhibitory concentration (IC50) values of Ag+, Co2+ and As5+ metal ions, which showed an inhibitory effect, were found to be 0.0044, 0.084 and 4.058 mM, respectively; and their inhibition constants (Ki) were found to be 0.0052 ± 0.00042, 0.087 ± 0.015700 and 4.833 ± 1.753207 mM, respectively. Tl+ not exhibited inhibitory effect on the enzyme activity.
2,3,7,8-Tetrachloro dibenzo-p-dioxin (TCDD), an endocrine-disrupting environmental pollutant, has been found to cause male reproductive toxicity. Glucocorticoids have been found to influence the metabolic pathway of TCDD. Stress, which affects the male reproductive function, is marked by an increase in the level and activity of glucocorticoids in the body. The present study was carried out to understand the effect of TCDD on testicular steroidogenesis and sperm antioxidant system under the influence of increased level of corticosterone in the body. Adult male rats were treated with either TCDD (100 ng/kg bw/ day) or corticosterone (3 mg/kg bw/day) or both for 15 days. Treatment with either TCDD or corticosterone was found to suppress the levels of steroidogenic acute regulatory protein and androgen-binding protein and reduce the activities of steroidogenic enzymes in testis while increasing oxidative stress in ventral prostate, seminal vesicles and epididymal sperm. In rats treated with both TCDD and corticosterone, the suppression of testicular steroidogenesis and increase in oxidative stress observed in ventral prostate, seminal vesicles and epididymal sperm were significant as compared to TCDD alone treated rats. The levels of Fas and FasL proteins were also increased in rats subjected to either TCDD or corticosterone treatment. In rats treated with both compounds, the increase observed in testicular levels of Fas and FasL was significant as compared to TCDD alone treated rats. Effect of TCDD on testicular steroidogenesis and antioxidant system of epididymal sperm may get enhanced under increased level of glucocorticoids in the body.
The present study was investigated to evaluate the uptake and accumulation of selenium (Se) by the stem cuttings of Portulaca oleracea L. grown in alfisol amended with various concentrations of Se. P. oleracea accumulated a maximum of 63.4 µg g-1 dry weight in a short growth period of 42 days. The order of accumulation of Se among the plant parts was leaves (31.5 μg g-1) > stems (16.4 μg g-1) > roots (15.5 μg g-1). The accumulation potential was fourfold higher than the plant available concentration of 15.2 μg g-1 of Se g-1 of soil (diethylenetriaminepentaacetic acid extracted). Although the plant was able to accumulate Se in their tissues, increase in Se concentrations in soil caused a concentration-dependent decrease in the growth rate of plants (regeneration of leaves, number of leaves, number of roots, root length, stem length and biomass).
Among the university students especially in adolescence period, smoking habits and unhealthy lifestyles are major problems in social life. In this study, it is intended to reveal smoking habits and lifestyles of the students from Suleyman Demirel University and to determine the effects of smoking and lifestyles on pulmonary functions. Materials and methods: Participants were 94 university students who were getting formal education in the Suleyman Demirel University central campus. Data were analysed by analysis of variance and chi-square tests. For all analysis, p value of <0.05 was considered significant. Results: Students’ mean age was 19.9 ± 0.9 years, and of all the students 74 (78.7%) were undergraduate students; remaining 20 (21.3%) were graduate students. Of all the students, 27 (28.7%), which comprised the largest group of the students, were living in state dormitory. Body mass index (BMI) was examined for the study group; according to BMI, body weight was generally within normal limits but 17.39% of girls’ were found to be underweight. Conclusions: Respiratory parameters can be affected by many factors. Smoking habit of university students can be prevented, and it is an important point that they have a healthy lifestyle both for their own health and for future generations.
Objectives: Occupational exposure to anaestethic gases has been suggested to induce auditory damages. The aim of this study is to investigate high-frequency audiometric responses in subjects exposed to anaesthetic gases, in order to highlight the possible effects on auditory system. Methods: The study was performed on a sample of 30 medical specialists of Messina University Anaesthesia and Intensive care. We have used tonal audiometry as well as high-frequency one. We have compared the responses with those obtained in a similar control group not exposed to anaesthetic gases. Results were compared statistically. Results: Results show a strong correlation (p = 0.000) between left and right ear responses to all the audiometric tests. The exposed and the control group run though the standard audiometry analysis plays different audiometric responses up only to higher frequencies (2000 HZ p = 0.009 and 4000 Hz p = 0.04); in high-frequency audiometry, as all other frequencies, the attention is drew to the fact that the sample groups distinguish themselves in a significantly statistic way (10,000 Hz p = 0.025, 12,000 Hz p = 0.008, 14,000 Hz p = 0.026, 16,000 Hz p = 0.08). The highest values are the ones related to exposed subjects both in standard (2000 Hz p = 0.01, 4000 Hz p = 0.02) and in high-frequency audiometry (10,000 Hz p = 0.011, 12,000 Hz p = 0.004, 14,000 Hz p = 0.012, 16,000 Hz p = 0.004). Conclusion: Results, even if preliminary and referred to a low-range sample, show an involvement of the anatomic structure responsible for the perception of high-frequency audiometric responses in subjects exposed to anaesthetic gases.
The accumulation of heavy metals such as lead (Pb), iron (Fe), zinc (Zn), cadmium (Cd), and chromium (Cr) was examined in crab (Scylla serrata) and shrimps (Penaeus semisulcatus, Penaeus indicus, and Penaeus monodon) collected from Pulicat lake that receives effluents from industries located in north Chennai, southeast coast of India. The results showed limited difference between crab and prawns as well as significant variations between the organs. Pb is the highly accumulated metal in both crab and shrimps, except P. monodon. The highest metal concentration was mostly found in the liver followed by other organs. The concentration of metals in edible parts (muscle) was within the permissible level and safe for consumption. However, the results of the study clearly indicate the biomagnification of metals in Pulicat lake.
The present study was undertaken to determine the effects of malathion exposure through maternal milk on oxidative stress, functional an metabolic parameters in kidney and liver of rat pups. We found that lactational exposure to malation (200 mg/kg, body weight (bw)) induced an oxidative stress status assessed by an increase in malondialdhyde (MDA) content, reflecting lipoperoxidation, a decrease in thiol groups’ content as well as depletion of enzyme activities as a superoxide dismutase (SOD) and catalase (CAT) on postnatal days (Pnds) 21 and 51. Moreover, the current study showed that malathion induced liver and kidney dysfunctions demonstrated by considerable increase in phosphatase alkaline (PAL), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities as well as total and direct bilirubin, creatinine urea and acid uric contents. We also observed an increase in triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and a decrease in high-density lipoprotein cholesterol (HDL-C) in the plasma of treated rat pups. These findings evidenced that malathion exposure during lactation through maternal milk of rats pups induced kidney and liver oxidative stress as well as functional and metabolic disorders that play a role in the development of others pathologies as cardiovascular diseases and cancers.
This work examines the crude methanolic extracts of three medicinally important plants native to Pakistan for potent phytotoxic activities and important phytochemicals. These plants include Euphorbia wallichii, Bergenia ciliata and Phytolacca latbenia. The phytotoxic effects were checked at 10,000, 1000, and 100 µg/ml against two economically important standard target species, Triticum aestivum (monocot representative) and Brassica napus (dicot representative). The phytotoxicity effects on seed germination, seedling growth and seedling weight were checked. A simple, cost-effective in vitro phytotoxicity assay (that uses petri plates) was used to evaluate the allelopathic properties of crude extracts. At highest concentration, extracts from all the three plants showed phytotoxic activities such that P. latbenia > E. wallichii > B. ciliata. In seedling growth, root length was affected more than shoot length, whereas among the target species B. napus was found to be more sensitive towards extracts when compared with T. aestivum. Phytochemical analysis showed that P. latbenia is rich in saponins and terpenoids, while E. wallichii and B. ciliata are rich in tannins, terpenoids and cardiac glycoside. P. latbenia also carries a moderate amount of cardiac glycosides.
The goal of this study was to explore the impact of 2-deoxglucose or malonate individually or in combination on the level of cell energy (adenosine-5'-triphosphate) and oxidative stress in 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary proliferation in rats. A total of 60 adult female Sprague Dawley rats were randomly divided into five groups (12 rats each): group I serves as the control group. Rats in groups (II–V) were administrated intragastrically a single dose of 50 mg/kg body weight (bw) of DMBA. A day after DMBA administration, rats in group III were injected intraperitoneally (ip) with 100 mg 2-deoxyglucose (2-DG)/kg bw daily. Rats in group IV were injected ip with 10 mg sodium malonate/kg bw daily. Rats in group V were injected ip with 100 mg 2-DG/kg bw and 10 mg sodium malonate/kg bw (treatment for 90 days). The results obtained showed that DMBA induced oxidative stress by decreasing the activities of glutathione reductase (GRase) and superoxide dismutase (SOD), glutathione peroxidase (GPx) and elevating the levels of malondialdehyde (MDA) and nitric oxide (NO) in mammary tissues when compared with control. The combined treatment protected against the previous deleterious changes by a significant elevation in the activities of GRase and SOD, GPx and lowering the levels of MDA and NO more potentially when compared with individual treatment. Apoptosis, as indicated by a significant release of cytochrome c from mitochondria into the cytosol, observed in DMBA-injected rats was positively significantly correlated with the elevation of the level of NO. These data explained the possible additive effect of 2-DG and malonate by depleting the cell energy by their protective effects against the earlier stages of carcinogenesis.
Objective: The purpose of the present study was to evaluate the effects of melatonin on biochemical and cardiovascular changes resulting from exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a polychlorinated dibenzo-para-dioxin.
Methods: A total of 24 Sprague-Dawley rats were divided equally into the following four groups: (1) control group was administered with 0.5 mL corn oil by gavage and 0.5 cc vehicle of melatonin (proportionally nine parts physiological serum + one part ethyl alcohol) intraperitoneally for 4 weeks, (2) the melatonin group was given 5 mg/kg/day melatonin intraperitoneally for 4 weeks, (3) the TCDD group was given 500 ng/kg/day TCDD by gavage for 4 weeks and (4) the TCDD + melatonin group was given TCDD (500 ng/kg/day) by gavage and melatonin (5 mg/kg/day) intraperitoneally simultaneously for 4 weeks. Systolic blood pressure was evaluated by the tail-cuff method. Vascular responses to phenylephrine and acetylcholine were evaluated in the isolated thoracic aortas.
Results: TCDD not only augmented the systolic blood pressure but also increased the contractile responses to phenylephrine in aorta. Melatonin reversed the blood pressure augmented by TCDD and decreased the contractile responses to phenylephrine in aorta. TCDD induced an increase in the malondialdehyde levels in kidney tissue and melatonin did not change it. Therefore, TCDD caused a decrease in glutathione levels in kidney tissues and melatonin reversed it.
Conclusion: Present data demonstrated that TCDD may lead to an increase in blood pressure via increased renal oxidative stress and vascular reactivity. However, melatonin might ameliorate the blood pressure disturbed by TCDD in part by decreasing the oxidant activity induced by TCDD.
Objective: Pentachlorophenol (PCP) is characterized as likely carcinogen of lymphoma and hematopoietic neoplasm. But the carcinogenicity to human was uncertain based on population studies. A systematic review was conducted to explore two kinds of associations, one was between the workers exposed to PCP with lymphoma and hematopoietic neoplasm, the other was between childhood lymphoma and leukemia with their parents exposed to PCP.
Methods: Systematic search for epidemiologic studies was carried out and the data were collected from MEDLINE database and from the reference lists of relevant studies. Data were extracted from 20 included studies published between 1986 and 2012.
Results: The meta-analysis suggested a significant association between lymphoma and workers’ occupational exposing to PCP, for the pooled odds ratio = 2.57 (95% confidence interval (CI) = 1.52–4.35). The subgroup analysis indicated significant association for non-Hodgkin’s lymphoma, but not for Hodgkin’s disease. The cohort studies also showed comparatively higher relative risk (RR) and standardized mortality ratio (SMR). Two of the cohort studies found increased RR as the cumulative exposure time added. Another cohort study discovered that the white males had significantly elevated non-Hodgkin’s lymphoma mortality (SMR = 1.98, 95% CI = 1.15–3.17), and males of other races had increased leukemia mortality (SMR = 4.57, 95% CI = 1.25–11.7). For the relationship of childhood leukemia and parental exposure to PCP, three published studies suggested an increased risk of childhood leukemia because of their parental exposure to PCP at the preconception period.
Conclusion: Our review provided the evidence that occupational exposure of workers to PCP might increase the risk of lymphoma and hematopoietic neoplasm in themselves and in their children.
The hypolipidemic effect of 10% fruit fibers in rats fed with high-fat diet (HFD) was evaluated. This study was conducted on a total of 50 male Albino rats divided into 10 equal groups fed with different types of dietary fruits. The feeding period lasted for 24 weeks. Fasting blood samples were collected and sera separated and subjected to lipid profile assay and atherogenic index. In addition, total antioxidant activity of different fruits was determined. The results obtained showed that pomegranate had higher content of antioxidants followed by apple, strawberry and guava compared with other fruits. Rats fed with 20% coconut oil showed a highly significant elevation in the levels of serum total cholesterol, low-density lipoprotein cholesterol and atherogenic factor while the level of high-density lipoprotein cholesterol was significantly decreased when compared with control rats. Histological examination revealed that there was a large lipid and cholesterol deposition in the livers of rats fed with HFD. The potential in lowering the levels of plasma total cholesterol and triglyceride is in the following order: pomegranate > apple > strawberry > guava > papaya > mandarin and orange. Accumulation of hepatic lipid droplets was diminished when compared with the HFD group. Also, antiatherogenic is better than the untreated groups. Accordingly these hypolipidemic effects may be due to high-fiber content and antioxidant activity of these fruits.
Rheumatic fever (RF) and rheumatic heart disease (RHD) are the multisystem autoimmune sequel of group A streptococci (GAS) infection of the upper respiratory passages, mainly tonsillopharyngitis. The major receptor on the surface of human palatine tonsil for GAS is fibronectin (FN; adhesin receptor). Early detection of RF susceptibility is considered as an important aim of this study. Therefore, the present study aimed to use FN immunoreactivity (FN-ir) as a marker for early detection of rheumatic susceptible children with palatine tonsil crypts surface epithelium. A total of 30 palatine tonsillar specimens were obtained from children aged from 3 to 15 years. Histological studies showed moderate vascular changes and more than four apparent epithelial disruptions in the crypt epithelium. FN-ir showed a significant increase in FN in the basal layers of surface epithelium, subepithelial connective tissue and interfollicular areas. Tonsils of children in rheumatic families showed significant increase in FN in subepithelial connective tissue areas with more than one apparent crypt epithelial disruption compared to normal children. We can conclude that FN plays a central role in the RF and differentially distributed in the functional compartments of the palatine tonsil in children with RHD, so FN-ir can be used as a marker for rheumatic susceptibility.
"Convolvulus hystrix Vahl" is a plant that has been known to Ancient Egyptians and to Arabs and its root was used traditionally as a purgative. Our attention was directed to the root bark as we observed that the largest part of the plant is deeply impeded underground. The work plan involved testing experimental animals for the influence of aqueous root bark extract on carbohydrate, fat and protein metabolisms as reflected on the growth and relevant laboratory metabolic assessment parameters. Proximate analysis showed high percentages of moisture (85%) and total lipids (7.2%) and surprising amounts of elements such as barium, strontium, rhodium and tellurium (1.7 mg, 3.1 mg, 8 mg and 9.1 mg/g ash, respectively). Random serum glucose value showed a significant decrease in the treated female group (p < 0.05). Serum total proteins of treated female group were found to be increased significantly (p < 0.001), while it was found to be decreased in the relevant treated male group (p < 0.01), together with a significant decrease in blood urea nitrogen (p < 0.05), with a significant increase in the serum creatinine (p < 0.05). Concerning serum fat metabolic parameters, a significant decrease in the serum triglycerides and high-density lipoproteins (p < 0.01 and p < 0.01, respectively) were found. We concluded that the presence of huge amount of polyphenolics such as tannins is responsible for the overall results documented as growth retarding and antinutritional factors. The results were motivating and pointed out to the possible opening of vast areas of research in the field of natural products. We recommend a series of biochemical and pharmacological studies concerning different parts of the plant as well.
Two freshwater fish, Rasbora sumatrana (Cyprinidae) and Poecilia reticulata (guppy; Poeciliidae), were exposed to a range of eight heavy metals (copper (Cu), cadmium (Cd), zinc (Zn), lead (Pb), nickel (Ni), iron (Fe), aluminium (Al), and manganese (Mn)) at varied concentrations for 96 h in the laboratory. Mortality was assessed and median lethal concentrations (LC50) were calculated. It was observed that the LC50 values increased with a decrease in mean exposure times, for all metals and for both fish types. The 96-h LC50 values for Cu, Cd, Zn, Pb, Ni, Fe, Al, and Mn were 0.006, 0.10, 0.46, 0.63, 0.83, 1.71, 1.53, and 5.71 mg/L for R. sumatrana and 0.038, 0.17, 1.06, 1.99, 15.62, 1.46, 6.76, and 23.91 mg/L for P. reticulata, respectively. The metal toxicity trend for R. sumatrana and P. reticulata from most to least toxic was Cu > Cd > Zn > Pb > Ni > Al > Fe > Mn and Cu > Cd > Zn > Fe > Pb > Al > Ni > Mn, respectively. Results indicated that Cu was the most toxic metal on both fish, and R. sumatrana was more sensitive than P. reticulata to all the eight metals.
This study is intended to examine the effects of administration of asymmetric dimethylarginine (ADMA) on the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-10. A total of 30 Wistar adult albino rats were used. Group I was administrated (n = 10) with 1 mg/kg/day of ADMA, group II (n = 10) was administrated with 2 mg/kg/day of ADMA and the control group was administrated (n = 10) with 0.9% sodium chloride. ADMA was intraperitoneally administrated for 7 days. The serum levels of IL-6, TNF-α and IL-10 were measured. There was a significant decrease in the levels of TNF-α, IL-6 and IL-10 in group I compared with that of the control group (p < 0.001). There was also a significant decrease in the levels of IL-10 in group II compared with that of the control group (p < 0.05) but the increase was much more distinct in the levels of IL-6 and TNF-α (p < 0.001). When comparing the groups by the doses given, no difference between the levels of IL-6 and IL-10 in groups I and II (p > 0.05) was observed; the levels of TNF-α in group II were significantly lower than those of group I (p < 0.05). A significant decrease in the serum levels of inflammatory cytokines IL-6, TNF-α and IL-10, after administration of 1 mg/kg/day and 2 mg/kg/day of ADMA, indicates that ADMA has an effect on inflammation. Increase in ADMA levels in the rats shows that the effects of inflammatory cytokines were suppressed.
Mycotoxins, the toxic products of molds, exposure causes serious adverse health problems in human, animals, and crops. Determining the potential genotoxic effects of these substances is, therefore, of great importance. We have evaluated the genotoxic toxicity of two trichothecenes – diacetoxyscirpenol (DAS) and T-2 toxin – using the wing somatic mutation and recombination test (SMART) in Drosophila melanogaster. The SMART is based on the principle that the loss of heterozygosis of recessive markers located on the left arm of chromosome 3 – multiple wing hairs (mwh) at the map position 0.3 and flare-3 (flr3) at the map position 38.8 – may occur through various mechanisms such as mitotic recombination, mutation, deletion, half-translocation, chromosome loss, and nondisjunction. Both the mycotoxins were administered to third instar larvae (72 ± 4 h old) at concentrations ranging from 5 to 40 μM. Based on our results, DAS and T-2 toxins does not exert genotoxic effects up to a concentration of 40 μM.
Snakebites are relatively rare medical emergency cases that might lead to serious consequences. This study aims to evaluate snakebite cases in terms of medical follow-up, antivenom therapy and antivenom reactions. Medical records of patients admitted to emergency department between January 1, 2006 and December 31, 2010 were retrospectively investigated. Snakebite-related cases of a total of 125 patients were included in the scope of the study. Of the total 125 cases, 54.4% were male and 45.6% were female. Most of cases (n: 65, 52%) were aged over 30 years, while the mean age was 34.87 ± 19.29 years. Snakebite-related applications to the emergency department were mostly seen in June with 27 cases. Upon admitting, all patients were recorded to be conscious and showing good general conditions; however, they suffered from pain and edema at the site of bite. Of all, 25 patients only suffered from bite injury and ecchymosis due to snakebite. The site of bite was upper extremities in 66 patients (52.8%), whereas it was lower extremities in 58 (46.4%). Of all, antivenom was unnecessary in 25 (20%) patients, while four antivenoms were administered to each of the 23 (18.4%) patients. Furthermore, six (4.8%) patients needed nine antivenom administrations for each. Anaphylaxis (n: 2, 1.6%), compartment syndrome (n: 2, 1.6%) and serum sickness (n: 1, 0.8%) encountered in remaining cases. Of all, 86 (68.8%) patients were hospitalized in the emergency department, while 25 (20.0%) patients were followed up by observation in emergency service. Only one patient was treated and followed up in intensive care unit. Implementation of antivenom therapy is considered unnecessary for the treatment of all snakebite cases. Antivenom reactions and number of related cases might be reduced by continuous close monitoring, appropriate prophylaxis and controlled slow infusion administration of medications.
Ethnopharmacological relevance: Lygodium flexuosum (Linn) Sw. is a climbing fern, and it is the sole genus in the family Lygodiaceae. It commonly grows epiphytically on moss covered tree trunks and branches as lithophytes on shady boulders along with moss. It has been reported as a traditional folkloric medicine for a variety of ailments particularly useful for carbuncles, inflammation, ulcer, various respiratory diseases, general disorders, muscle sprains and acts as panacea for wounds. However, there are no scientific reports on wound healing activity of the plant L. flexuosum (Linn) Sw.
Aim of the study: To explore the protective effect of L. flexuosum against excision, incision and dead space wounds models in experimental rats.
Methods: Wistar albino rats of either sex weighing between 180 and 220 g were topically treated with extract formulated in ointment using simple ointment BP as base. Ointments, 4% and 5% (w/w), were applied once daily in excision wound model. L. flexuosum ethanolic extract was given orally at a dose of 100, 200 and 400 mg/kg in incision and dead space wound healing models. Rats of standard groups were treated with 0.2% nitrofurazone ointment topically. The percentage wound contraction, epithelization time in excision wound model; breaking strength in incision wound model and wet and dry granulation weight, hydroxyproline content were measured.
Results: Topical application of L. flexuosum in excision wound model increased the percentage of wound contraction, and the epithelization time was decreased. In the incision wound model, the breaking strength of wounds increased and in dead space model the weight of dry and wet granuloma of wounds and hydroxyproline was increased. Conclusively, the data of present study indicated that the leaf extract of L. flexuosum accelerated wound healing in rats and thus supports its traditional use.
In this study, 70 Wistar rats were randomly divided into seven equal groups (six experimental and one control), which consisted of animals belonging to both sexes. Different combinations of insecticides were administered daily to the experimental groups (group 1: cypermethrin + piperonyl butoxide (PBO); group 2: alphacypermethrin + PBO; group 3: deltamethrin + PBO; group 4: cypermethrin + PBO + tetramethrin; group 5: alphacypermethrin + PBO + tetramethrin; and group 6: deltamethrin + PBO + tetramethrin) for 28 days. During the study period, mortality and serious clinical findings were not observed in any animal. However, feed consumptions decreased in groups 1 and 3 (p < 0.05). Red blood cells, white blood cells, and hemoglobin levels, especially in cypermethrin and alphacypermethrin groups (groups 1, 2, and 4), were found to be higher than the control group (p < 0.05). Furthermore, biochemical changes related to liver, kidney functions, and protein metabolism occurred in males of almost all the groups. Relative liver and kidney weights of the male animals increased in the cypermethrin and alphacypermethrin groups (p < 0.05). The most common finding observed during the histopathological examination of all the experimental groups was centrilobular degeneration in the liver. It was concluded that although clinical symptoms were not observed, synthetic pyrethroid, synergist, and knockdown agent combinations might cause serious abnormalities when administered in certain doses in mammalians.
The aim of the present study was to assess the influence of curcumin on liver regeneration after partial hepatectomy (PH) in rats. A total of 24 male Sprague Dawley rats were divided into three groups: sham-operated (SH), PH, and PH + curcumin; each group contains eight animals. The rats in curcumin-treated groups were given curcumin (in a dose of 100 mg/kg body weight) once a day orally for 7 days, starting 3 days prior to hepatectomy operation. At 7 days after resection, liver samples were collected. The malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) levels were estimated in liver homogenates. Moreover, histopathological examination, mitotic index (MI), proliferating cell nuclear antigen labeling, proliferation index (PI), transferase-mediated 2'-deoxyuridine, 5'-triphosphate nick end-labeling assay, and apoptotic index (AI) were evaluated at 7 days after hepatectomy. As a result, curcumin significantly increased MI and PI and significantly decreased AI in PH rats. Additionally, curcumin remarkably inhibited MDA elevation, restored impaired antioxidant SOD activity and GSH level and also attenuated hepatic vacuolar degeneration and sinusoidal congestion. These results suggested that curcumin treatment had a beneficial effect on liver regenerative capacity of the remnant liver tissue after hepatectomy, probably due to its antioxidative, antiapoptotic, and proliferative properties.
Ifosfamide (IFO) is a highly effective chemotherapeutic agent for treating a variety of pediatric solid tumors. However, its use is limited due to its serious side effect on kidneys. The side-chain oxidation of IFO in renal tubular cells produces a reactive toxic metabolite that is believed to be responsible for its nephrotoxic effect. Therefore, this study was carried out to investigate the possible underlying mechanisms that may be involved in IFO-induced nephrotoxicity, including free radical generation and the possible role of alpha lipoic acid (ALA) versus N-acetylcysteine (NAC) in protection against this toxicity. Male albino rats were injected intraperitoneally with saline, IFO (50 mg/kg daily for 5 days), IFO + ALA (100 mg/kg daily for 8 days) and IFO + NAC (200 mg/kg daily for 8 days). Kidney malondialdehyde, nitric oxide and glutathione contents and serum biochemical parameters and histopathological analysis were determined. Both ALA and NAC markedly reduced the severity of renal dysfunction induced by IFO. NAC was more nephroprotective than ALA. This study suggests that oxidative stress is possibly involved in the IFO-induced nephrotoxicity in rats. The study also suggests the potential therapeutic role for ALA and NAC against IFO-induced nephrotoxicity.
This study was carried out to investigate comparatively some serum mineral levels of cigarette smokers. A total of 25 nonsmokers (control group) and 50 long-term cigarette smokers (smoking for at least 15 years; smoker group) were participated in the study. Subjects were between 25 and 40 years old. Control and smoker groups were matched for age, sex and body mass index status. The blood samples were taken from smokers and nonsmokers after 12 h of fasting period. The levels of zinc (Zn), copper (Cu), iron (Fe), magnesium (Mg), calcium (Ca), potassium (K), chlorine (Cl), sodium (Na) and phosphorus (P) were measured by autoanalyzer using commercial kits. Student’s t test was used to compare the control and smoker groups, and p < 0.05 indicated a significant difference. Pearson’s correlation coefficient was used to demonstrate the relationship among parameters in smoker and control groups. Although there was no statistical difference (p > 0.05) between the groups regarding the levels of K, P, Mg, Na, Cl, Zn, Fe, Ca and Cu, some positive correlations were observed in controls but not in smokers. Therefore, it was concluded that smoking does not affect the serum mineral levels. However, it may negatively affect some important positive correlations among minerals observed in healthy individuals.
Although it has been suggested that high-resolution computed tomography (HRCT) scans can be obtained when plain radiographs are equivocal for the presence of interstitial lung fibrosis (ILF) caused by inhalation of dust, such as silica, asbestos fibres, etc., the specificity of the findings remains in question. The present study was carried out to compare the relative efficacy of chest radiography by conventional method and HRCT in evaluating ILF which included 22 workers exposed to fibrogenic dust, who were subjected to clinical examination, pulmonary function testing, posteroanterior chest radiography and HRCT. In the six subjects who had findings suggestive of ILF on HRCT, four had normal chest x-ray (CXR) while one each has been diagnosed as having tuberculosis and ILF on CXR. The agreement analysis between HRCT and CXR suggests that there was a poor agreement between HRCT and CXR (kappa = 0.34).
Laboratory experiments were performed to determine phytotoxic potentials of white top (Lepidium draba) methanol extracts (root, stem and leaf) on germination and early growth of corn (Zea mays) and redroot pigweed (Amaranthus retroflexus). Furthermore, the effects of different methanol extracts of L. draba on the phytohormone (indole-3-acetic acid (IAA), gibberellic acid (GA), abscisic acid (ABA) and zeatin) levels of corn and redroot pigweed were investigated. It was observed that all concentrations of methanol extracts of root, stem and leaf of L. draba inhibited germination, radicle and plumule elongation when compared with the respective controls. Besides this, the degree of inhibition was increased in concert with increasing concentrations of extracts used. On the other hand, phytohormone levels changed with the application of different extract concentrations. Comparing with the control, the GA levels significantly decreased while the ABA levels increased in all the application groups. Zeatin and IAA levels showed changes depending upon the applied extracts and concentrations.
It has been asserted that consumption of dietary cholesterol (Chol) raises atherosclerotic cardiovascular diseases and that Chol causes an increase in free radical production. Hypercholesterolemic diet has also been reported to cause changes in the antioxidant system. In our study, different doses of Juniperus communis Linn (JCL) oil, a tree species growing in Mediterranean and Isparta regions and having aromatic characteristics, were administered to rats; and the levels of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and thiobarbituric acid reactive substances assay (TBARS) were examined in the heart tissue of rats. In this study, 35 Wistar Albino male adult rats weighing approximately 250–300 g were used. The rats were divided into five groups of seven each. The control group was administered normal pellet chow, and the Chol group was administered pellet chow including 2% Chol, while 50 JCL, 100 JCL, and 200 JCL groups were administered 50, 100, and 200 mg/kg JCL oil dissolved in 0.5% sodium carboxy methyl cellulose, respectively, in addition to the pellet chow containing 2% Chol, by gavage. After 30 days, the experiment was terminated and the antioxidant enzyme activities were examined in the heart tissue of rats. While consumption of dietary Chol decreases the activities of SOD, GSH-Px, and CAT in heart tissue of rats (not significant), administeration of 200 mg/kg JCL oil in addition to Chol led to a significant increase in the activity of antioxidant enzymes. Administering Chol led to a significant increase in TBARS level. Administering 100 and 200 mg/kg JCL oil together with Chol prevented significantly the increase in lipid peroxides. As a result of the study, JCL oil showed oxidant–antioxidant effect in the heart tissue of rats.
The manufacturing processes in chip industries are complex, and many kinds of raw materials and solvents of different nature are used, most of which are highly toxic and dangerous. During the machine preventive maintenance period, these toxic and harmful substances will escape from the sealed reaction chamber to the clean workshop environment and endanger the health of the workers on-site, resulting in occupational diseases. From the perspective of prevention, the spread and prediction of hydrochloric acid (HCl) that escaped from the metal-etching chamber during maintenance were studied in this article. The computational fluid dynamics technology was used for a three-dimensional numerical simulation of the indoor air velocity field and the HCl concentration field, and the simulation results were then compared with the on-site monitoring data to verify the correctness and feasibility. The occupational hazards and control measures were analyzed based on the numerical simulation, and the optimal control measure was obtained. In this article, using the method of ambient air to analyze the occupational exposure can provide a new idea to the field of occupational health research in the integrated circuit industry and had theoretical and practical significance.
The effects of trona (Kaun), a food additive, on the redox status of the liver and kidney of male Wistar rats were investigated. A total of 60 male rats (145 ± 2.52 g) were grouped into four: A, B, C and D, where group A (the control) received 1 mL of distilled water orally while those in groups B, C and D (test groups) received orally, same volume of trona preparation corresponding to 100, 200 and 400 mg/kg body weight, respectively, for 28 days. Administration of trona significantly reduced (p < 0.05) alkaline phosphatase activity in the liver and kidney with corresponding increases in the serum enzyme. Acid phosphatase activity increased significantly (p < 0.05) in the liver and kidney with no significant change (p > 0.05) in the activity of the serum enzyme. The activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and the levels of reduced glutathione, vitamins C and E in the liver and kidney of the animals decreased significantly (p < 0.05). In contrast, malondialdehyde and lipid hydroperoxide of trona-treated animals increased significantly (p < 0.05) in liver and kidney. Overall, data from this study revealed that trona exhibited its toxic effect by suppressing or depleting the antioxidant systems and increasing the risk of attack by oxidants generated either from its metabolites or from other in vivo means on the rat cellular system.
In this article, the genotoxic and antigenotoxic effects of methanol extract of Evernia prunastri (Huds.) Willd. (MEP) were studied using WP2, Ames (TA1535 and TA1537) and sister chromatid exchange (SCE) test systems. The results obtained from bacterial test systems demonstrated that MEP has strong antimutagenic potencies on TA1537 and WP2 strains. The highest inhibition rates for MEP on TA1537 and WP2 strains were 37.70% and 69.70%, respectively. According to the SCE test system, MEP reduced the genotoxic effects of aflatoxin. In order to clarify the mechanism underlying the antigenotoxic effects of MEP, the antioxidants were determined. Cotreatments of 5, 10 and 20 µg/mL concentrations of MEP with aflatoxin B1 decreased the frequencies of SCE and the malondialdehyde level and increased amount of superoxide dismutase, glutathione and glutathione peroxidase which were decreased by aflatoxin. The data obtained from this work have clearly shown that MEP has significant antigenotoxic effects which are thought to be partly due to the antioxidant activities and antioxidant inducing capability of MEP. This is the first report indicating the antigenotoxic activities of MEP against several mutagen agents such as N-methyl-N'-nitro-N-nitrosoguanidine, acridin and aflatoxin.
Heavy metal pollution is a serious environmental and health problem. The negative effects of heavy metals that can enter human body can be reduced by the addition of some supplements. In this study, the effects of lead (Pb), cadmium (Cd) and copper (Cu) on the hematological parameters in Wistar rats in the absence and presence of lipoic acid and glutathione were analyzed. Pb, Cd and Cu intoxication significantly affected the hematological parameters of treated animals. The main effects in the case of Pb and Cd intoxication were decreased values of erythrocytes, hemoglobin and hematocrit (up to 30% and 20% for these two metals, respectively) compared with the control group. Cu intoxication caused decrease in hematocrit, thrombocytes, mean cell volume values (c.a. 15%) and slight decrease in the erythrocyte number, while the value of hemoglobin increased (c.a. 7%). The treatment with lipoic acid and glutathione reduced the toxic effects of these metals in all cases.
The present study was conducted on 80 pesticide male sprayers (42 nonsmokers and 38 smokers). Our aim was to estimate the smoking effects on blood lipids and oxidant/antioxidant status in pesticide sprayers. Results revealed that cholesterol, low-density lipoprotein (LDL) and glutathion peroxidase (GPx) enzyme were significantly higher in the 38 smoker sprayers than in the 42 nonsmoker sprayers. Cholesterol and LDL were correlated with smoking index and high-density lipoprotein (HDL), superoxide dismutase (SOD) enzyme and zinc (Zn) were inversely correlated with duration of pesticides' exposure. In nonsmokers, LDL and cholesterol were negatively correlated with SOD and correlated with malondialdehyde (MDA), and cholesterol was negatively correlated with Zn. HDL was negatively correlated with MDA in all the sprayers, but was correlated with GPx in smokers and with Zn in nonsmokers. In smokers, LDL was negatively correlated with GPx, HDL was negatively correlated with MDA and triglycerides and very-low-density lipoprotein were negatively correlated with Zn. MDA was negatively correlated with SOD, GPx and Zn. Smoking and pesticide exposure could be responsible for hyperlipidemia and oxidative stress. Therefore, improvement in the antioxidant status is mandatory for pesticide sprayers especially the ones who smoke.
The aims of this study were to clarify the effects of dietary boric acid or borax, as a boron (B) source, on hormonal status (leptin, insulin, triiodothyronine (T3), and thyroxine) and some biochemical parameter levels as glucose, carnitine, nonesterified fatty acids, and betahydroxybutyric acid in rats. A total of 30 Sprague-Dawley male rats were divided into three equal groups: the animals in the first group (control) were fed with a standard rodent diet containing 6.4 mg B/kg, and the animals in the experimental group were fed with a standard rodent diet added with boric acid and borax (100 mg B/kg) throughout the experimental period of 28 days. The B compounds especially borax decreased leptin, insulin, and glucose levels, whereas increased T3 and carnitine levels in plasma. In addition, body weight of rats was found to be low in the boric acid group at the end of 4 weeks. Consequently, our results demonstrate that B supplementation (100 mg/kg) in diet decreases body weight, leptin, and insulin, whereas increases T3 levels in plasma, so enhances the metabolic activity of rats. Between the B compounds used in this study, it was found that borax had a greater effect on hormonal status than boric acid.
This study was designed to investigate the reproductive toxicity of aluminium sulphate and the therapeutic effects of administration of zinc sulphate and vitamin E individually or in combination against the toxic effect caused by aluminium (Al) in male albino rats. The animals were divided into five groups: group 1 received distilled water and served as control; group 2 received only aluminium sulphate (50 mg/kg body weight (b.w.)); group 3 received aluminium sulphate (50 mg/kg b.w.) plus zinc sulphate (50 mg/kg b.w.); group 4 received aluminium sulphate (50 mg/kg b.w.) and vitamin E (15 mg/kg b.w.); group 5 received aluminium sulphate plus a combination of zinc sulphate and vitamin E in similar doses as above. Doses were administered orally once daily for 45 consecutive days. The results revealed that aluminium sulphate induced significant decrease in body weight gain and testis weight and significant increase in Al level in both serum and testes of male rats. Biochemical analysis showed significant decrease in serum total protein and phospholipids levels, while serum total lipid was significantly elevated post Al treatment. In addition, significant decrease in total protein, phospholipids and cholesterol levels in the testes of Al-treated rats was recorded. The data also showed significant decrease in the levels of serum testosterone, leutinizing hormone and follicle stimulating hormone and significant increase in the level of serum prolactin in Al-intoxicated rats. Moreover, histological examination showed that aluminium sulphate caused apparent alterations in the testicular structure of the treated animals. Treatment with zinc sulphate and vitamin E individually or in combination ameliorated the harmful effects of Al, which was proved histopathologically by the noticeable improvement in the testicular tissues. We can conclude that the tested dose of aluminium sulphate induced toxic effect on the reproductive system of male albino rats and the treatment with zinc sulphate and/or vitamin E alleviated these toxic effects. In some cases, vitamin E exerted a more potent effect, while in other cases, the more potent effect is related to zinc sulphate and the combination of both at most of the recorded data.
Arsenic is one of the most hazardous substances in the environment known to cause toxicity in multiple organs. Cell adhesion, morphological alterations, cell proliferation, terminal deoxyuridine triphosphate nick-end labeling (TUNEL) and caspase-3/CPP32 fluorometric protease assay were important biomarkers to assess apoptosis in cells. This study aimed to evaluate arsenic-induced apoptosis in the hepatocytes of rat and its protective efficacy with coadministration of ascorbic acid (AA) and Pleurotus florida lectin (PFL) individually. Results of the present study also showed that arsenic caused cytotoxicity by elevating morphological alterations, TUNEL-positive nuclei, caspase-3 activity and DNA damage and reducing cell adhesion and cell proliferation in a time-dependent manner. The apoptosis in hepatocytes was reverted to normal value after coadministration of mushroom lectin in arsenic-exposed rat. The study provided significant evidence that PFL has antiapoptotic property against arsenic-induced toxicity. The beneficial effect of PFL was proportional to its duration of exposure. Retard activities of superoxide dismutase and catalase, enhanced lipid peroxidation as well as protein carbonyl in erythrocytes caused by arsenic could also be maintained toward normalcy by supplementation of AA and PFL. These antioxidative effects were exhibited in a time-dependant manner. In rat, treatment with AA and PFL prevented alteration of plasma enzyme activities caused by arsenic. The results concluded that treatment with PFL has significant role in protecting animals from arsenic-induced erythrocytic damage. This finding might be of therapeutic benefit in people suffering from chronic exposure to arsenic from natural sources, a global problem especially relevant to millions of people on the Indian subcontinent.
In the present study, the effects of xenoestrogen 4-nonylphenol (4-NP) and 17β-estradiol (E2) on the synthesis of vitellogenin (VTG) in immature male yellowfin seabream (Acanthoparus latus) were assessed to determine the potential use of this species as a biological model for studying endocrine disrupters in the Musa estuary in southern seawaters of Iran. A total number of 104 fish were injected by 10, 50, 100, 150 and 200 µg g-1 week-1 of 4-NP and 2 µg g-1 week-1 of E2, and their blood plasma was obtained for biochemical analysis on days 0, 7 and 14. The hepatosomatic index (HSI) of each fish was also recorded at each sampling time. The results showed that 4-NP significantly induced VTG synthesis in A. latus, which was detected by gel electrophoresis as two major protein bands (~210 and 191 KDa). The induction of VTG was also determined indirectly by measuring the alkali-labile phosphate, total plasma calcium and protein. All of these VTG indicators significantly increased in the plasma of 4-NP- and E2-treated fish. Meanwhile, a significant dose-dependent increase was observed in HSI, indicating the activation of hepatic VTG production in 4-NP- and E2-injected fish. Furthermore, the plasma alanine aminotransferase and aspartate aminotransferase concentrations significantly increased in 4-NP-treated fish, presumably reflecting a situation of hepatic tissue damage due to 4-NP toxicity. Based on the results, it is suggested that A. latus could be used successfully as a model species for future studies of endocrine disrupting contaminants in the Musa estuary.
Pulmonary complications due to mustard gas exposure range from no effect to severe bronchial stenosis. Pulmonary function tests (PFTs) and respiratory symptoms in chemical war victims were studied 23–25 years after exposure to sulfur mustard (SM). Respiratory symptoms were evaluated in a sample of 142 chemical war victims and 120 control subjects with similar age from the general population using a questionnaire including questions on respiratory symptoms in the past year. PFT values were also measured in chemical war victims before and 15 min after the inhalation of 200 µg salbutamol and baseline PFT in controls. All chemical war victims (100%) reported respiratory symptoms. Wheezing (66.19%), cough (64.78%), and chest tightness (54.4%) were the most common symptoms and only 15.5% of chemical war victims reported sputum (p < 0.01 for sputum and p < 0.001 for other symptoms compared with control group). In addition, 49.3% of chemical war victims had wheeze in chest examination, which were significantly higher than control group (p < 0.001). The severity of respiratory symptoms was also significantly higher than control subjects (p < 0.05 for sputum and p < 0.001 for other symptoms). All the PFT values were also significantly lower in chemical war victims than that in control subjects (p < 0.001 for all cases). In addition, all the PFT values improved significantly after the inhalation of 200 µg salbutamol (p < 0.05–p < 0.001). These results showed that chemical war victims, 23–25 years after exposure to chemical warfare have higher frequencies and severity of respiratory symptoms. PFT values were also significantly reduced among chemical war victims, which showed reversibility due to the inhalation of 200 µg salbutamol.
Aluminum (Al) metal is considered one of the most benign industrial metals. Although the harmful effects of Al on respiratory health have been denied by some studies, others reported its noxious effect on the lung through spirometric measurements. This work aimed at studying the effect of Al fumes on pulmonary functions of occupationally exposed workers. It investigated the possible relationship between inhalation exposure to Al fumes and levels of C-reactive protein (CRP) and alpha-1-antitrypsin (A1AT). The study participants comprised a group of 56 male Al workers with a mean duration of occupational exposure of 10.1 ± 9.5 years and 52 male participants who were not exposed to Al fumes as the control group. All participants filled a questionnaire, underwent full clinical examination and their spirometric pulmonary functions were measured. Blood samples were collected for the determination of serum CRP and A1AT and urine samples for measuring Al. Results revealed that urinary Al (UAl) was significantly higher in Al workers compared with controls (p < 0.05). However, spirometric measures showed no significant difference between the exposed group and the controls. A1AT was significantly lowered in Al workers compared with the controls (p < 0.000). Serum CRP was positive in only two (3.6%) of the exposed workers. Smokers of both groups (exposed and controls) showed significantly higher UAl and lower A1AT compared with nonsmokers. There was only significant negative correlation between the duration of exposure and A1AT (p < 0.05). There was a positive significant correlation between smoking index (SI) and UAl. There was also significant negative correlation between SI and some of the pulmonary function tests namely the percentage of predicted forced vital capacity, forced expiratory volume in the first second and peak expiratory flow in the exposed group. Those correlations point to the importance of the combined effect of smoking and Al exposure on the impairment of lung functions. The study recommends the determination of CRP and A1AT in Al-exposed workers. It is expected that those parameters may undergo changes before reduction in pulmonary functions takes place.
The present study examined the heart rate turbulence (HRT) and heart rate variability (HRV) parameters in healthy young smokers (<40 years) to assess the effects of smoking on cardiac autonomic function. The study included 75 smokers with a history of habitual smoking for at least 1 year (41 males and 34 females; mean age, 29.3 ± 7.3 years) and 30 nonsmokers (hospital staff; 16 males and 14 females; mean age, 29.0 ± 6.1 years). Addiction to smoking was evaluated using the modified Fagerström test for nicotine-dependence index (NDI). HRT, HRV, basic clinical and echocardiographic, and Holter test parameters were compared between groups. No significant differences between the two groups were found in the basic clinical and echocardiographic variables. Turbulence onset (TO) was significantly higher in the smoking group than in the controls, and turbulence slope was significantly lower in the smokers, than in the controls (p < 0.05). Standard deviation of all normal-to-normal (NN) interval index (SDNNI) was the only HRV parameter that was significantly different between the smoking and control groups (p < 0.05). The NDI was positively correlated with the TO (p < 0.05). Smoking impairs the baroregulatory function in healthy young smokers, particularly the HRT parameters and SDNNI. Our findings highlight the importance of complete smoking cessation.
The purpose of this article was to investigate the levels of metals, cadmium, lead, and zinc, in Western reef heron (Egretta gularis) (n = 15) in order to (1) examine the sex-related variation in trace metal accumulation and (2) determine the significant differences between the metal concentrations in the kidney, liver, and pectoral muscle. Bird samples were collected from throughout the Hara biosphere reserve of southern Iran, during November and December 2010 and the concentration of metals were measured using a Shimadzu AA 680 flame atomic absorption spectrophotometer. The overall cadmium, lead and zinc concentrations means were measured as 0.8 ± 0.1, 3.4 ± 1.1, and 29.4 ± 12.9 μg/g for kidney; 0.7 ± 0.1, 2.2 ± 0.5, and 65.9 ± 20.7 μg/g for liver; and 0.2 ± 0.1, 2.2 ± 0.7, and 17.6 ± 12.9 μg/g for pectoral muscle, respectively. The results showed that with the exception of cadmium in liver, there were no significant differences between males and females (t test, p > 0.05). In the contrast, the results indicated metal concentrations differed significantly in kidneys, livers, and pectoral muscles among tissues in Western reef heron (one-way analysis of variance, p < 0.001).
Biosorption of copper (Cu) ions from aqueous solutions has been studied in a batch system using a Bacillus species AEJ-89 isolated from Maranjab desert soil. The optimum conditions of biosorption were determined by investigating the initial pH, contact time, and the initial concentrations of metal ions at constant temperature (25°C). The maximum biosorption of Cu ions was observed at pH 5.0 ± 0.1. Biosorption equilibrium times for Cu (II) ions were observed in 30 min. The maximum biosorption capacities of Cu (II) ions on Bacillus species AEJ-89 were determined to be 0.48 mmol g-1 at 200 mg l-1 concentration. The experimental adsorption data were fitted to Langmuir isotherm model. The interactions between metal ions and functional groups on the cell wall surface of the biomass were confirmed by Fourier transform infrared spectroscopy analysis. Cu (II) ions were removed from metal-laden biomass after desorption treatments by the addition of different desorbing solutions. The results indicated that the bacterial isolate Bacillus species AEJ-89 is a suitable biosorbent for the removal of Cu (II) ions from aqueous solutions.
Methomyl (MET) is used worldwide in agriculture and health programs. Besides its advantages in the agriculture, it causes several toxic effects. The objective of this study was to examine the potential ability of vitamin C and/or selenium (Se), to alleviate the oxidative damage parameters, against MET-induced changes in blood biochemical markers and oxidative damage in liver and kidney of male Wistar rats. The animals were randomized into five groups of eight each: group I served as control rats; group II received MET (8 mg/kg body weight (BW)) in drinking water; group III received both MET and vitamin C (200 mg/kg BW; by intraperitoneal injection); group IV received both MET and Se (0.6 mg/100 g BW). Animals of group V were treated with MET, vitamin C and Se. A significant increase in the levels of hepatic markers enzymes (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and lactate dehydrogenase) was determined. Furthermore, renal markers such as urea and creatinine were increased in MET-treated rats. Additionally, serum cholesterol and triglycerides were significantly enhanced. Exposure of rats to MET caused significant increase in malondialdehyde levels, thus causing a drastic alteration in antioxidant defense system, particularly in the activities of catalase and glutathione-S-transferase and glutathione peroxidase. However, simultaneous supplementation with vitamin C and Se restored these parameters partially. In conclusion, the results of the current study revealed that MET-induced toxicity caused perturbations of some biochemical parameters, lipid peroxidation and alterations in the antioxidant enzymes in liver and kidney homogenates. Administration of vitamin C and Se exhibited protective effect by inhibiting MET-induced toxicity in liver and kidney.
Effect of standardized Bacopa monniera (BM; family: Scrophulariaceae) extract (100 and 300 mg/kg) against sodium fluoride (NaF; 100 and 200 ppm)-induced behavioural, biochemical, and neuropathological alterations in mice was evaluated. Akinesia, rotarod (motor coordination), forced swim test (depression), open field test (anxiety), transfer latency (memory), cholinesterase (ChE), and oxidative stress (superoxide dismutase, catalase, glutathione peroxidase, and lipid peroxidation) were determined in mice treated with NaF for 30 days alone and in combination with BM. NaF induced motor incoordination, depression, and memory impairment, and these were prevented by coadministration of BM in mice. However, NaF did not alter the weight gain, feed/water consumption, and anxiety profile. Suppression of ChE levels and increased oxidative stress were observed in mice treated with NaF. Coadministration of BM significantly improved the memory, ChE levels, and antioxidant enzymes but failed to alter the fluoride levels in NaF-treated mice. Histopathological studies revealed that BM protected the neuropathological alterations induced by NaF.
In this study, potential genotoxic effects of ethyl methanesulfonate (EMS) that caused mutagenicity in a variety of organisms were tried to resolve by the methanol and chloroform extract of Echium amoenum (EAmet and EAchl) Fisch. & C.A. Mey. from the family of Boraginaceae, which is an endemic plant, and is used as an alternative treatment among public in Iran. Somatic mutation and recombination test with Drosophila wing was used to determine the genotoxic and antigenotoxic effects in our investigations. For this purpose, 3-day-old transheterozygous larvae of mwh/flr3 genotype of Drosophila melanogaster were used in all our experiments. The larvae were fed chronically on the Drosophila instant medium (DIM) including 1 ppm EMS. However, in another application group, different concentrations (1, 2 and 4 ppm) of EAmet and EAchl were added to DIM including 1 ppm EMS (EMS + EAmet and EMS + EAchl). Then, for the matured individuals, wing preparates were prepared within the mediums that include control group that has only DIM, negative control group that contains dimethyl sulfoxide and application groups in different concentrations that contain EMS, EMS + EAmet and EMS + EAchl. Clone induction frequency for the normal wing phenotype of EMS application group was observed to be 2.00. In the EMS + EAmet application group, the value of 1 ppm EAmet is 1.49, value of 2 ppm EAmet is 1.08 and value of 4 ppm EAmet is 0.72; in the EMS + EAchl application group, the value of 1 ppm is EAchl 1.33, value of 2 ppm EAchl is 0.67 and value of 4 ppm EAchl is 0.56 were determined. This decrease observed between EMS and all application groups in terms of total induction frequency is statistically significant (p < 0.05). These results concluded that chloroform extracts were more effective than the methanol extracts of E. amoenum.
Traditionally, the herbal drugs are well established for their therapeutic benefits. Depending upon their geographical sources sometimes the trace and heavy metals’ content may differ, which may lead to severe toxicity. So, the toxicological and safety assessment of these herbal drugs are one of the major issues in recent days. Eight different plant species including Aloe vera, Centella asiatica, Calendula officinalis, Cucumis sativus, Camellia sinensis, Clitoria ternatea, Piper betel and Tagetes erecta were selected to determine their heavy and trace metals content and thereby to assure their safer therapeutic application. The trace and heavy metals were detected through atomic absorption spectrometry analysis. The selected medicinal plant materials were collected from the local cultivated regions of West Bengal, India, and were digested with nitric acid and hydrochloric acid as specified. Absorbance was measured through atomic absorption spectrometer (AA 303) and the concentration of different trace and heavy metals in the plant samples were calculated. The quantitative determinations were carried out using standard calibration curve obtained by the standard solutions of different metals. The contents of heavy metals were found to be within the prescribed limit. Other trace metals were found to be present in significant amount. Thus, on the basis of experimental outcome, it can be concluded that the plant materials collected from the specific region are safe and may not produce any harmful effect of metal toxicity during their therapeutic application. The investigated medicinal plants contain trace metals such as copper (Cu), chromium (Cr), manganese (Mn), iron (Fe) and nickel (Ni) as well as heavy metals such as arsenic (As), lead (Pb) and mercury (Hg), which were present within the permissible limit.
Paraphenylene diamine (PPD) hair dye poisoning is a common health problem in the Middle East and Indian subcontinent. It is the most common cause of suicide intent especially among females. We hereby present a 27-year-old female who presented with a clinical feature of PPD poisoning due to a suicidal attempt, and she died soon after arrival. She had survived a previous suicide attempt with PPD 4 years before. This time she also intentionally tried to kill her four children using PPD. One child died, one recovered after dialysis for acute kidney injury and the other two survived without any further intervention. This case illustrates that PPD poisoning may be used in filicide and suicide intent and that all patients who committed suicide should be reviewed and assessed by clinical psychiatrist.
The present study was carried out to evaluate the effects of exposure at different doses of acephate on hematology, blood biochemistry, oxidative stress and immune system of Wistar rats. The experiment was carried out on 40 Wistar rats, which were divided in four groups. Animals of the three treatment groups were given with different sublethal doses (1/40th, 1/20th, 1/10th of lethal dose 50 value) of acephate by oral gavage. The hematology, blood biochemistry, oxidative stress marker, humoral immune response and cell-mediated immunity were evaluated following acephate exposure. Significant alteration in hematological parameters was not observed following different doses of acephate; however, significant alteration in alkaline phosphatase, gamma glutamyl transferase, acetyl cholinesterase, lipid peroxidase and superoxide dismutase was observed in medium- and high-dose group animals. Nonsignificant decrease in antibody titer in animals exposed to high dose has been observed compared with animals of control group. However, significant alteration in cell-mediated immunity was not observed in animals treated with acephate at different doses.
Background: A variety of HIV-related endocrine dysfunctions including adrenal, gonadal and thyroid disorders have been reported. We aimed to compare between the markers of thyroid function in newly diagnosed HIV-infected patients and healthy volunteers as a control group. The prevalence of the thyroid abnormalities in HIV-infected patients was assessed and the levels of thyroid autoantibodies were also determined.
Methods: A total of 100 newly diagnosed HIV-infected patients having a CD4 cell count of 180–350 cells/mm3 were enrolled in the study. Same number of healthy volunteers were also included for comparison. Measurements of thyroid function tests including thyroid-stimulating hormone (TSH), free thyroxin and free triiodothyronine levels beside thyroid autoantibodies, including antithyroglobulin (ATBG) and antithyroid peroxidase (ATPO), were carried out for all patients and volunteers.
Results: In total, 70% of HIV-infected patients had normal thyroid function tests when compared with control individuals, while 30% of HIV-infected patients had abnormal thyroid function. Of the 30 cases, 11 cases had abnormal TSH values, with increased TSH predominant (7% of HIV cases) than decreased TSH (4% of patients) values. Incidence of thyroid abnormalities ranging from hypothyroidism (subclinical and overt: 6% and 1%, respectively) to hyperthyroidism (2%) and nonthyroidal illness (9%) were estimated in HIV-infected patients. The values of thyroid autoantibodies were almost normal in HIV-infected patients, except the three cases presented with elevated ATBG, indicating that thyroid abnormalities were not due to elevated ATBG and ATPO.
Conclusions: Thyroid hormones are of great importance and due to high prevalence of thyroid function abnormality, it is recommended that thyroid function tests should be monitored in all HIV-infected patients before starting the treatment.
In a study on villagers settled on the outskirts of the Taurus Mountains and whose source of living is thyme, it was revealed that the villagers excessively consumed thyme by adding it to their tea and many of their foods; high incidences of anemia was found among these villagers. In this study, 42 male adult Wistar albino rats weighing 200–250 g were used. The rats were divided to six equal groups as follows: control, cholesterol (Chol), 80 mg/kg Origanum onites Labiatae (OOL), 80 mg/kg Thymbra spicata Labiatae (TSL), 80 mg/kg Satureja cuneifolia Labiatae (SCL), and 160 mg/kg TSL, and each group consisted of seven rats. The control group was fed with normal pellet feed. The Chol group and all the other groups, except for the control group, were fed with 2% cholesterol-containing pellet feed. Physiological serum of 4 ml was given to the control and Chol group, wheile 80 mg/kg of thymes tea was given to the OOL group, TSL group, and SCL group, and 160 mg/kg of thymes tea was given to the TSL group by means of a gavage for 30 days. In the blood samples, the hematologic parameters and the biochemical parameters of serum glucose, blood urea nitrogen, creatinine, total protein, albumin, iron (I), total iron-binding capacity, aminotransferase aspartate, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, triglyceride, and oxidized LDL levels were examined. The kidney and liver tissues were examined histopathologically. The results of the study showed that different types of thymes had an antihypercholesterolemic effect. In addition to the anemic effect detected in group TSL and the mild granular degeneration found in the liver of 80 mg/kg SCL group, distinct granular degeneration was observed in 160 mg/kg TSL group.
Holothuria polii (Delle Chiaje, 1823) (Holothuriidae) is a sea cucumber inhabiting Mediterranean Sea coast of Egypt. The bioactive compound of its tegument has antifungal, antibacterial and antiparasitic effects. The present study aims to elucidate the structure of the bioactive material of H. polii for pharmacological and chemotaxonomic purposes. Furthermore, the study demonstrates its efficacy as a cytotoxic agents against two tumor cell lines HCT116 (colon adenocarcinoma cell line) and MCF7 (breast adenocarcinoma cell line). The biological active compound of the ethanol extract has been characterized by means of infrared (IR), proton-nuclear magnetic resonance (1H NMR), ultraviolet–visible (UV–Vis) and mass spectra. Protein profile was carried out using sodium dodecyl sulfate polyacrylamide gel electrophoresis. Cytotoxic activity was carried out according to sulforhodamine-B assay. IR, 1H NMR, UV–Vis and mass spectra showed that the extracted bioactive material is a nonsulfated hexaosides called bivittoside. This glycoside is composed of aglycone and a glycosidic chain (carbohydrate chain) enclosed with six sugar units, including xylose, glucose, 3-O-methylglucose and quinovose. There were no traces of dissolved proteins. The preliminary cytotoxic assay of bivittoside exhibited significant cytotoxic activity against two types of cultured tumor cell lines of HCT116 and MCF7. The half-maximal inhibitory concentration was 17.4 µg/ml and 18 µg/ml for MCF7 and HCT116, respectively. Although H. polii belongs to the genus Holothuria, the lacking of sulfate group and the fact that it contains up to six monosaccharides make it different from this genus. The present study suggests separation of H. polii from its genus to a new one. On the other hand, results support the hypothesis that H. polii bioactive compound has an antitumor effect.
In vitro genotoxic effects of antioxidant additives, such as citric acid (CA) and phosphoric acid (PA) and their combination, as well as antimicrobial additives, such as benzoic acid (BA) and calcium propionate (CP), on human lymphocytes were determined using alkaline single-cell gel electrophoresis. There was a significant increase in the DNA damage in human lymphocytes after 1 h of in vitro exposure to CA, PA, BA and CP (200, 25–200, 50–500, 50–1000 μg/mL, respectively). The combination of CA and PA significantly increased the mean tail intensity at all the concentrations used (25–200 μg/mL) and significantly increased the mean tail length mainly after higher concentrations (100 and 200 μg/mL). Data in this study showed that the concentrations of food additives used induce DNA damage and PA was the most genotoxic and CA was less genotoxic additives among them.
Formaldehyde is a major industrial chemical and has been extensively used in the manufacture of synthetic resins and chemicals. Numerous studies indicate that formaldehyde can induce various genotoxic effects in vitro and in vivo. A recent study indicated that formaldehyde impaired antioxidant cellular defences and enhanced lipid peroxidation. Selenium is an important antioxidant. We hypothesized that reactive oxygen species (ROS) and lipid peroxidation are involved in formaldehyde-induced genotoxicity in human lung cancer cell line, A549 cell line. To test the hypothesis, we investigated the effects of selenium on formaldehyde-induced genotoxicity in A549 cell lines. The results indicated that exposure to formaldehyde showed the induction of DNA–protein cross-links (DPCs). Formaldehyde significantly increased the malondialdehyde levels and decreased the activities of superoxide dismutase and glutathione peroxidase. In addition, the activations of necrosis factor-B (NF-B) and activator protein 1 (AP-1) were induced by the formaldehyde treatment. The pretreatment with selenium counteracted the formaldehyde-induced oxidative stress, ameliorated DPCs and attenuated the activation of NF-B and AP-1 in A549 cell lines. All the results suggested that the pretreatment with selenium attenuated the formaldehyde-induced genotoxicity through its ROS scavenging and anti-DPCs effects in A549 cell lines.
Di(2-ethylhexyl) phthalate (DEHP), the most abundant phthalate in the environment, is known to be a reproductive toxicant. Considering the therapeutic significance of medicinal plants, this study was conducted to evaluate the effects of administration of celery oil on DEHP-induced testicular toxicity. The experiment was carried out for 8 weeks on 36 male rats that were divided equally into six groups. Group 1 was kept as normal control (given vehicle), while rats of group 2 were administered orally 200 mg/kg/day of celery oil. Groups 3 and 5 were orally given 500 and 1000 mg DEHP/kg/day, respectively. Groups 4 and 6 were treated with similar doses of DEHP as in groups 3 and 5 plus celery oil (200 mg/kg/day). Body and testicular weights, sperm parameters, serum hormones (testosterone, follicle-stimulating hormone, luteinizing hormone and estradiol), antioxidant enzymes (superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT)) and expression of cytochrome P450 aromatase (CYP19) messenger RNA (mRNA) were investigated at the end of 8th week. Treatment with DEHP alone resulted in a significant decrease in body and testicular weights, sperm parameters and serum hormone levels when compared with control. On the other hand, testicular antioxidant enzymes showed a significant dose-dependent increase. The expression of CYP19 mRNA was significantly reduced by increasing the doses of DEHP. Administration of celery oil along with DEHP partially prevented the decrease in body and testicular weights and enhanced epididymal sperm count, serum hormone levels and the expression of CYP19 mRNA along with diminution in the activities of SOD, GPx and CAT enzymes. The obtained results showed that the celery improved the testicular alterations induced by DEHP in albino rats.
Most pomegranate (Punica granatum Linn., Punicaceae) fruit parts are known to possess enormous antioxidant activity. The present study was carried out to determine the phenolic and flavonoid contents of Derik pomegranate juice and determine its effect against carbon tetrachloride (CCl4)-induced toxicity in rats. Animals were divided into four groups (n = 6): group I: control, group II: CCl4 (1 ml/kg), group III: CCl4 + pomegranate juice and group IV: CCl4 + ursodeoxycholic acid (UDCA). Treatment duration was 4 weeks, and the dose of CCl4 was administered once a week to groups II, III and IV during the experimental period. CCl4-treated rats caused a significant increase in serum enzyme levels, such as aspartate aminotransferase, alanine aminotransferase and total bilirubin, and decrease in albumin, when compared with control. Administration of CCl4 along with pomegranate juice or UDCA significantly reduces these changes. Analysis of lipid peroxide (LPO) levels by thiobarbutiric acid reaction showed a significant increase in liver, kidney and brain tissues of CCl4-treated rats. However, both pomegranate juice and UDCA prevented the increase in LPO level. Histopathological reports also revealed that there is a regenerative activity in the liver and kidney cells. Derik pomegranate juice showed to be hepatoprotective against CCl4-induced hepatic injury. In conclusion, present study reveals a biological evidence that supports the use of pomegranate juice in the treatment of chemical-induced hepatotoxicity.
The prevalence of diabetes mellitus in the world is steadily increasing. Oxidative stress contributes to the development of diabetic complications, including diabetic haematological changes. Lichens are used as food supplements and are also used as possible natural antioxidant, antimicrobial and anticancer agents. We hypothesized that antioxidant activity of lichens may decrease hyperglycaemia-induced oxidative stress and prevent the development of diabetic complications, including abnormality in haematological condition. Therefore, the effects of Cetraria islandica water extract (CIWE) and Pseudevernia furfuracea water extract (PFWE) on the haematological parameters of rats with type 1 DM were investigated for the first time in the present study. Control Sprague-Dawley or streptozotocin (STZ)-induced diabetic rats were either untreated or treated with water lichen extracts (5–500 mg/kg body weight (bw)/day) for 2 weeks, starting at 72 h after STZ injection. On day 14, animals were anaesthetized and haematological and metabolic parameters were determined between control and experimental groups. In addition, the total oxidative stress (TOS), a specific indicator of oxidative stress, and the total antioxidant capacity (TAC) were measured by biochemical studies. In diabetic rats, CIWE of 250–500 mg/kg bw dose showed more prominent results when compared with doses of PFWE for TAC. The results obtained in the present study suggested that the antioxidant activities of lichens might be the possible reason behind the observed antihaematological status. However, the protective effect of lichen extracts were inadequate on diabetes-induced microcytic hypochromic anaemia. In addition, the extracts have no effect on metabolic complications. Our experimental data showed that high doses of CIWE and PFWE alone have no detrimental effect on blood cells and TOS status of plasma. Hence, they are safe and suitable for different administration routes.
Aim: Carbon monoxide (CO) intoxication can be serious and is reported to be the cause of more than half of all fatal intoxications. In this study, we aimed to identify its genotoxic effects based on sister chromatid exchange (SCE).
Materials and methods: CO-poisoned patients presented to the emergency services department were identified. Their demographic characteristics, vital findings, laboratory markers, source of CO gas, risk factors, and smoking habits were recorded. The genotoxic effect was assessed using the SCE method.
Results: A total of 38 patients were recruited. Their ages ranged from 16–64 years (mean: 29.79 ± 10.92 years). In all the cases, the source of CO gas was a flash heater. The mean carboxyhemoglobin (COHb) level was 25.05 ± 7.15%. Of all the patients, 12 (31.6%) had a the Glasgow Coma Scale (GCS) scores of less than 15, and an important negative correlation was found between the GCS and COHb level (r = -0.825; p < 0.001). Genotoxicity investigations revealed a significantly higher SCE frequency among patients with high COHb levels compared with that of control subjects with physiological COHb levels (p < 0.001). However, no correlation between increased SCE frequency and COHb level was found (r = 0.16; p = 0.34).
Conclusion: CO poisoning was shown to result in genotoxicity via an increase in the frequency of SCE. This study is the first to demonstrate a genotoxic effect of CO independent of other chemicals.
The exposure of gastric mucosa to damaging factors, such as ethanol and some therapeutic drugs, produces pathological changes: inflammatory process, hemorrhagic erosions and even acute ulcers. Ankaferd blood stopper (ABS) comprises a standardized mixture of five different plant extracts. The purpose of our present investigations is to explain the participation of reactive oxygen species in acute gastric mucosal damage by acetylsalicylic acid (ASA) and the effects of new hemostatic agent ABS. Experiments were carried out on 23 male Wistar rats. To assess gastric mucosal damage, biochemical and histopathological data were used. The colorimetric assays were used to determine the malondialdehyde (MDA) and superoxide dismutase (SOD) activity. The level of myeloperoxidase (MPO) activity, the level of nitric oxide (NO) and the proinflammatory cytokine tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay technique. We demonstrated that the biological effects of ROS were estimated by measuring the tissue and plasma levels of MDA, the products of lipid peroxidation, as well as the activity of SOD and the scavenger of ROS produced by ASA in the experiment group. Moreover, it was found that MPO activity as well as NO and TNF-α levels also demonstrated significant improvement by ABS treatment. The pathogenesis of experimental ASA-induced mucosal damage in rat stomach includes the generation of ROS that seems to play an important role, due to the generation of lipid peroxides, accompanied by the impairment of antioxidative enzyme activity of cells. ABS appeared to attenuate the oxidative and inflammatory changes caused by ASA-induced gastric mucosal damage in rats.
Objective: To investigate the effects of T-2 toxin on testosterone biosynthesis in mouse Leydig cells.
Methods: Leydig cells isolated from clean and healthy Kunming male mice, whose concentration was adjusted to 5 x 105/mL and the purity identified by the modified 3β-hydroxysteroid dehydrogenase staining method, were used to establish a primary Leydig cell culture model. Blank control group (treated with 0 ng/mL human chorionic gonadotropin (hCG) and 0 mol/L T-2 toxin), inductive control group (treated with 10 ng/mL hCG and 0 mol/L T-2 toxin), low-dose T-2-toxin-exposure group (treated with 10 ng/mL hCG and 10-9 mol/L T-2 toxin), middle-dose T-2 toxin-exposure group (treated with 10 ng/mL hCG and 10-8 mol/L T-2 toxin) and high-dose T-2-toxin-exposure group (treated with 10 ng/mL hCG and 10-7 mol/L T-2 toxin) were designed. The testosterone level was measured after 24 h incubation.
Results: After 24 h culture in liquid medium containing serum, the fresh isolated Leydig cells grew well and the purity exceeded 90%. By inducing 10 ng/mL hCG, the testosterone level of Leydig cells increased significantly and the difference compared with the blank control was of statistical sense. Compared with the inductive control group, the testosterone level of Leydig cells decreased, and the difference was of statistical sense in all T-2-toxin-exposure groups. Furthermore, the decrease was due to the increase in the dosage of T-2 toxin.
Conclusions: T-2 toxin can directly decrease the testosterone biosynthesis in the primary Leydig cells derived from the mouse testis.
Objective: In our previous study, we reported that the micron-sized nickel oxide nanoparticle agglomerates induced neutrophil infiltration and the gene expression of the cytokine-induced neutrophil chemoattractant (CINC)-2αβ in a rat lung. In this study, we examined the expression of the CINCs family in the lung using the same rat model exposed to micron-sized nickel oxide nanoparticle agglomerates.
Methods: The count median diameter of nickel oxide nanoparticle agglomerates suspended in saline was 1.34 μm (primary diameter: 8.41 nm). Male Wistar rats received an intratracheal instillation of 1 mg (3.3 mg/kg) of nickel oxide nanoparticles and were dissected at 3 days, 1 week, 1 month, 3 months, and 6 months after the instillation. The negative control group received an instillation of saline. The concentration of CINC-1 in the lung and the bronchoalveolar lavage fluid (BALF), CINC-2αβ in the BALF, and CINC-3 in the lung and the BALF was examined.
Results: The concentration of CINC-1 was elevated at 3 days, 3 months, and 6 months in the lung tissue and from 3 days to 6 months in the BALF. The concentration of CINC-2αβ was elevated from 3 days to 3 months in the BALF. The concentration of CINC-3 was also elevated at 3 days, 1 week, 3 months, and 6 months in the lung tissue. Infiltration of neutrophil and alveolar macrophage was observed mainly in the alveoli during the observed time period.
Conclusion: These results suggest that CINC-1 to -3 were totally involved in the lung injury caused by micron-sized nickel oxide nanoparticle agglomerates.
The aryl hydrocarbon receptor (AHR) is one of the principal xenobiotic, nuclear receptor that is responsible for the early events involved in the transcription of a complex set of genes comprising the CYP450 gene family. In the present computational study, homology modelling and molecular docking were carried out with the objective of predicting the relationship between the binding efficiency and the lipophilicity of different polychlorinated biphenyl (PCB) congeners and the AHR in silico. Homology model of the murine AHR was constructed by several automated servers and assessed by PROCHECK, ERRAT, VERIFY3D and WHAT IF. The resulting model of the AHR by MODWEB was used to carry out molecular docking of 36 PCB congeners using PatchDock server. The lipophilicity of the congeners was predicted using the XLOGP3 tool. The results suggest that the lipophilicity influences binding energy scores and is positively correlated with the same. Score and Log P were correlated with r = +0.506 at p = 0.01 level. In addition, the number of chlorine (Cl) atoms and Log P were highly correlated with r = +0.900 at p = 0.01 level. The number of Cl atoms and scores also showed a moderate positive correlation of r = +0.481 at p = 0.01 level. To the best of our knowledge, this is the first study employing PatchDock in the docking of AHR to the environmentally deleterious congeners and attempting to correlate structural features of the AHR with its biochemical properties with regards to PCBs. The result of this study are consistent with those of other computational studies reported in the previous literature that suggests that a combination of docking, scoring and ranking organic pollutants could be a possible predictive tool for investigating ligand-mediated toxicity, for their subsequent validation using wet lab-based studies.
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by elevated oxidative stress and inflammatory biomarkers. The severe side effects of drug used during such disease necessitate the search for new and safe approaches. Food is a rich source of antioxidants and anti-inflammatory bioactive constituents including phenolic compounds, polyunsaturated fatty acids, phytosterols, toccopherols, and carotenoids. We have a series of publications dealing with the anti-inflammatory activity of different food extracts (as nutraceuticals) in experimental animals (acute and chronic inflammation model) and in clinical study (RA patients). Fish oil, primrose oil, extracts of black cumin, fenugreek, liquorice, coriander, tomato, carrot, sweet potato, broccoli, green tea, rosemary, hazelnut, walnut, wheat germ, and date in addition to the probiotic Bifidobacterium bifidum were the nutraceuticals studied. During these studies, changes in inflammatory biomarkers (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), seromucoids, fibrinogen, tumor necrosis factor-α (TNF-α), prostaglandin E2), oxidative stress (malondialdehyde), antioxidant status (total antioxidant capacity, vitamin C, vitamin E, retinol, β-carotene), the level of copper (Cu) and zinc (Zn) and colonic microflora in response to the administration of nutraceuticals have been assessed. Results of these studies showed that the majority of nutraceuticals studied possess beneficial effect toward chronic inflammatory diseases, which might be due to the presence of one or more of the above-mentioned phytochemicals. Conclusion: Anti-inflammatory and antioxidant nutraceuticals may serve as complementary medicine for the management of RA.
In addition to the primary components of alloys, approximately 5% of the formulation may contain other metals, including lead (Pb), cadmium (Cd), arsenic, manganese (Mn), iron, phosphorus, and nickel. Workers in the foundries are exposed to several compounds; therefore, it is important to assess the levels of injury that may reflect an additive, synergistic, or antagonistic effect caused by these compounds. The mean values of the environmental evaluation of the facilities range from 16.65 to 40.31 µg m-3 for Pb, 0.99 to 1.73 µg m-3 for Cd, and 0.91 to 1.70 µg m-3 for Mn. The mean values of the metal concentrations for furnace, mold, melting, and automatic melting activities range from 15.37 to 19.26 µg m-3 for Pb, 7.07 to 9.14 µg m-3 for Cd, and 8.83 to 16.00 µg m-3 for Mn. Biological samples were divided into two groups: control (n = 38) and exposed (n = 45). The obtained data are3.41 ± 3.40 and 14.89 ± 7.82 µg dL-1 for Pb, 0.90 ± 0.80 and 1.91 ± 1.90 µg g-1 creatinine for Cd, and 0.51 ± 0.40 and 3.17 ± 1.93 µg g-1 creatinine for Mn. Statistical analysis showed significant differences (p < 0.05). Positive linear correlations were established between metal concentrations in the air and the biological matrixes: Pb (r = 0.68; p < 0.001), Cd (r = 0.81; p = 0.17), and Mn (r = 0.12; p < 0.03). Regression analysis showed that professional activities can interfere with element exposure profiles in occupational settings. The analysis in the event of exposure to metals in these companies allowed investigating whether the simultaneous exposure leads to biological damage even if the levels of the compounds are within the exposure limits that are considered to be safe.
This study was designed to investigate whether exposure to short-term extracorporeal shock wave lithotripsy (ESWL) produces histologic changes or induces apoptosis in the kidney, adrenal glands or diaphragm muscle in rats. The effect of shock waves on the kidney of male Wistar rats (n = 12) was investigated in an experimental setting using a special ESWL device. Animals were killed at 72 h after the last ESWL, and the tissues were stained with an in situ Cell Death Detection Kit, Fluorescein. Microscopic examination was performed by fluorescent microscopy. Apoptotic cell deaths in the renal tissue were not observed in the control group under fluorescent microscopy. In the ESWL group, local apoptotic changes were observed in the kidney in the area where the shock wave was focused. The apoptotic cell deaths observed in the adrenal gland of the control group were similar to those observed in the ESWL groups, and apoptosis was occasionally observed around the capsular structure. Apoptotic cell deaths in the diaphragm muscle were infrequently observed in the control group. Apoptosis in the ESWL group was limited to the mesothelial cells<sc>.</sc> This study demonstrated that serious kidney, adrenal gland and diaphragm muscles damage occurred following ESWL, which necessitated the removal of the organ in the rat model. It is recognized that the ESWL complications related to the kidney, adrenal gland and diaphragm muscles are rare and may be managed conservatively.
Edible mushrooms (EMs) are nutritionally rich source of proteins and essential amino acids. In the present study, the antioxidant activity via 1,1-diphenyl-2-picrylhydrazyl (DPPH) and antimicrobial potential in EMs (Pleurotus ostreatus, Morchella esculenta, P. ostreatus (Black), P. ostreatus (Yellow) and Pleurotus sajor-caju) were investigated. The DPPH radical scavenging activity revealed that the significantly higher activity (66.47%) was observed in Morchella esculenta at a maximum concentration. Similarly, the dose-dependent concentrations (200, 400, 600, 800 and 1000 µg) were also used for other four EMs. Pleurotus ostreatus exhibited 36.13% activity, P. ostreatus (Black (B)) exhibited 30.64%, P. ostreatus (Yellow (Y)) exhibited 40.75% and Pleurotus sajor-caju exhibited 47.39% activity at higher concentrations. Furthermore, the antimicrobial potential were investigated for its toxicity against gram-negative bacterial strains (Escherichia coli, Pseudomonas aeroginosa, Salmonella typhi, Klebsiella pneumonia, Erwinia carotovora and Agrobacterium tumifaciens), gram-positive bacterial strains (Bacillus subtilis, Bacillus atrophaeus and Staphylococcus aureus) and a fungal strain (Candida albicans) in comparison with standard antibiotics. Antimicrobial screening revealed that the ethanol extract of P. ostreatus was active against all microorganism tested except E. coli. Maximum zone of inhibition (13 mm) was observed against fungus and A. tumifaciens. P. sajor-caju showed best activities (12.5 mm) against B. subtilis, B. atrophaeus and K. pneumonia. P. ostreatus (Y) showed best activities against P. aeroginosa (21.83 mm), B. atrophaeus (20 mm) and C. albicans (21 mm). P. ostreatus (B) exhibited best activities against C. albicans (16 mm) and slightly lower activities against all other microbes except S. typhi. M. esculenta possess maximum activities in terms of inhibition zone against all microorganisms tested except S. typhi.
The goal of this study was to evaluate the possible protective effects of melatonin against cholestatic oxidative stress, liver damage and hepatocyte apoptosis in the common rats with bile duct ligation (BDL). A total of 24 male Wistar albino rats were divided into three groups: control, BDL and BDL + received melatonin; each group contains eight animals. Melatonin-treated BDL rats received daily melatonin 100 mg/kg/day via intraperitoneal injection. The application of BDL clearly increased the malondialdehyde (MDA) levels and decreased the superoxide dismutase (SOD) and glutathione (GSH) activities. Melatonin treatment significantly decreased the elevated tissue MDA levels and increased the reduced SOD and GSH enzyme levels in the tissues. The changes demonstrate that the bile duct proliferation and fibrosis in expanded portal tracts include the extension of proliferated bile ducts into lobules, mononuclear cells and neutrophil infiltration into the widened portal areas as observed in the BDL group. The data indicate that melatonin attenuates BDL-induced cholestatic liver injury, bile duct proliferation and fibrosis. The α-smooth muscle actin (α-SMA) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in the BDL were observed to be reduced with the melatonin treatment. These results suggest that administration of melatonin is a potentially beneficial agent to reduce liver damage in BDL by decreasing oxidative stress.
Biomarkers are key molecular or cellular events that give an indication whether there is a threat for disease, whether a disease already exists, or how such disease may develop in an individual case. The discovery of polymorphisms in genes that function in the metabolism of chemicals and in DNA repair has demonstrated the importance of understanding the phenomenon of genetic susceptibility in a population. Polymorphisms in DNA repair genes as an important component of the individual susceptibility to the development of cancer and various hereditary diseases have been commonly studied, since these genes have critical roles in maintaining genome integrity. Furthermore, the evaluation of cancer risk depends on the level of exposure to carcinogenic factors as well as on the genetic codes of the individual. This approach is supported by studies that present positive association between these polymorphic genes and cancers. Although 8-oxoguanine DNA glycosylase 1 (OGG1) is one of the promising biomarker candidates of cancer susceptibility, there are also some controversial results. Epidemiological studies show that the OGG1 might be a biomarker of susceptibility for various cancers; however, the small sample size and difference in the eligibility criteria for inclusion of subjects and sources might limit the studies to demonstrate the association between the OGG1 Ser326Cys polymorphism and the risk of cancer. Thus, meta-analyses may provide more valuable and reliable data to demonstrate the potential of OGG1 Ser326Cys DNA repair enzyme polymorphisms that could be the biomarkers of susceptibility of cancer. Our aim in this review is to compile published studies, including some controversial results on the association between the OGG1 Ser326Cys polymorphism and the risk of cancer.
Arsenic trioxide (As2O3) is an effective drug in the treatment of leukaemia and many solid tumours. In clinical trials, arsenic therapy is closely associated with hepatic toxicity. The present study was designed to investigate the efficacy of omega-3 fatty acid against As2O3-induced hepatotoxicity. A 4 mg/kg body weight (bw) of As2O3 was orally administered to Wistar male rats for 45 days. Hepatotoxicity was evaluated by biochemical tests, antioxidant assays and histopathological examinations. Arsenic accumulation was found in the liver tissue of rats treated with As2O3. Hepatoprotective efficacy of omega-3 fatty acid was analysed by the combination therapy with As2O3. In vivo studies revealed a significant rise in lipid peroxidation with concomitant decline in reduced glutathione, glutathione-dependant antioxidant enzymes and antiperoxidative enzymes in the liver tissue of rats treated with arsenic. The supplementation of omega-3 fatty acid at a dose of 50 mg/kg bw with As2O3 offers ameliorative effect against hepatocellular toxicity. Omega-3 fatty acid maintained hepatic marker enzymes, antioxidant enzymes and decreased lipid peroxidation. The combination treatment clearly reduced the hepatic structural abnormalities such as haemorrhage, necrosis and cholangiofibrosis in the rats treated with arsenic. This study concludes that the omega-3 fatty acid might be useful for the protection against As2O3-induced hepatotoxicity.
The present study was designed to investigate the antinociceptive potential of Vernonia cinerea (VC) on vincristine-induced painful neuropathy in rats. A chemotherapeutic agent, vincristine (50 μg/kg intraperitoneally for 10 consecutive days), was administered for the induction of neuropathic pain in rats. The painful behavioral changes were assessed using hot plate, acetone drop, paw pressure, Von Frey hair and tail immersion tests to assess the degree of hyperalgesic and allodynic pain sensation in paw and tail. Tissue biomarker changes including thiobarbituric acid reactive substances (TBARSs), reduced glutathione (GSH) and total calcium levels were estimated in sciatic nerve tissue samples to assess the degree of oxidative stress. Histopathological changes were also observed in transverse sections of rat sciatic nerve tissue. Ethanolic extract of VC leaves and pregabalin were administered for 14 consecutive days from day 0 (day of surgery). Pregabalin served as a positive control in the present study. Vincristine administration resulted in a significant reduction in painful behavioral changes along with a rise in the levels of TBARS, total calcium and decrease in GSH levels when compared with the normal control group. Furthermore, significant histopathological changes were also observed. Pretreatment with VC significantly attenuated vincristine-induced development of painful behavioral, biochemical and histological changes in a dose-dependent manner, which is similar to that of pregabalin-pretreated group. The attenuating effect of VC in vincristine-induced nociceptive painful sensation may be due to its potential of antioxidative, neuroprotective and calcium channel inhibitory action.
Phosgene (CG) is an industrial chemical used to make plastics, rubbers, dyestuff, and pesticides. Although the inhalation of CG is relatively uncommon, its accidental exposure can lead to acute lung injury (ALI). Ulinastatin, a urinary trypsin inhibitor, has been emerged to use for the treatment of acute inflammatory state of a number of organs including the lung. In this study, we examined the pathogenic changes in the lungs after the inhalation of CG gas and also examined the effect of ulinastatin treatment in reversing these changes in rats. We found that the rats exposed to CG gas at a dose of 5.0 g/m3 for 5 min led to ALI after 6 h. The signs of lung injury include pulmonary edema, hemorrhage, and cellular infiltration in pulmonary alveoli. In addition, interleukin-15 (IL-15) and intercellular adhesion molecule-1 (ICAM-1) were significantly increased in CG-inhaled animals. Ulinastatin administration at 1 h postexposure significantly reduced the intensity of all the pathological changes in the lungs of these CG-exposed animals. Ulinastatin at a dose of 400 U/g was shown to decrease the total number of cells in bronchoalveolar lavage fluid and the levels of IL-15 and ICAM-1 in the serum. We also found that the structure of the lung was protected by ulinastatin treatment. Thus, our data suggest that ulinastatin can be used as an effective drug for the treatment of CG-induced ALI. The serum levels of IL-15 and ICAM-1 can be used as the markers of lung injury after exposure to CG and may also serve as useful therapeutic targets at an early stage. The effects of long-term treatment of ulinastatin and the mechanisms by which ulinastatin decreases the infiltration of blood cells and reduces cytokines need further investigation.
The main purpose for this study was to monitor ambient air particles and metallic elements (Mn, Fe, Zn, Cr, Cu and Pb) in total suspended particulate (TSP) concentration and dry deposition. In addition, the calculated/measured dry deposition flux ratios of ambient air particles and metallic elements (Mn, Fe, Zn, Cr, Cu and Pb) were evaluated using Woods’ model at urban and wetland areas for the 2009–2010 period. The results indicated that the mean highest concentrations of metallic elements Mn, Fe, Zn, Cr, Cu and Pb in TSP were found in Chang-Hua (urban) sampling site. And as for the two characteristic sampling sites, the Woods’ model exhibits better dry deposition of particulates of 18 µm particle size than the rest of the other particle sizes at any sampling site in this study. The average calculated/measured flux ratios for two seasons (summer and fall) by using Woods model at 2.5, 10 and 18 µm particles sizes were also studied. The results indicated that the average calculated/measured flux ratios orders for two seasons of various particles sizes were all displayed as Fe > Mn > Zn > Cu > Cr > Pb > particle. And these calculated/measured flux ratios orders were Fe > Mn > Cu > Zn > Cr > Pb > particle and were Fe > Mn > Zn > Cu > Cr > particle > Pb, during spring and winter seasons, respectively. Finally, in the spring and summer seasons of Gao-Mei (wetland) sampling site, the average calculated/measured flux ratios using Woods’ model was found to be 2.5, 10 and 18 µm, showing the order of the calculated/measured flux ratios to be Fe > Cu > Zn > Mn > Cr > Pb > particle. And the calculated/measured flux ratio orders were Fe > Zn > Mn > Cu > Cr > particle > Pb and were Fe > Cu > Zn > Mn > Cr > particle > Pb for fall and winter season, respectively.
Objective: This study is aimed to investigate the efficacy of erdosteine usage in acetaminophen-induced liver damage and to compare it with N-acetyl cysteine (NAC) in the treatment and prevention of liver toxicity due to overdose of acetaminophen.
Methods: The rats were separated into the following six groups of seven rats each: control group; acetaminophen (1 g/kg, orally); acetaminophen (1 g/kg, orally) + erdosteine (150 mg/kg/day, orally); acetaminophen (1 g/kg, orally) + NAC (140 mg/kg loading dose, followed by 70 mg/kg, orally); NAC (140 mg/kg loading dose, followed by 70 mg/kg, orally); erdosteine (150 mg/kg/kg, orally), subsequently. In all the groups, potential liver injuries were evaluated using biochemical and hematological analyses, oxidant–antioxidant parameters and histopathological parameters.
Results: In acetaminophen-treated group, levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total oxidant status (TOS) in the blood, prothrombin time (PT) and international normalized ratio (INR) were significantly increased when compared with controls. However, total antioxidant capacity (TAC) and glutathione (GSH) levels were decreased in group treated with acetaminophen, when compared with control group. Levels of AST, ALT and TOS, PT and INR were decreased in groups treated with NAC and erdosteine after acetaminophen administration, but the levels of TAC and GSH were increased. Histopathological improvements were observed in the groups treated with NAC and erdosteine after acetaminophen administration.
Conclusion: The present study demonstrated that, in the prevention of liver damage induced by acetaminophen intoxication, an early treatment with a single dose of erdosteine was beneficial instead of NAC administration.
There is growing evidence that the effects of microcystin-LR (MC-LR) are closely related to apoptosis. This study utilized microarray to identify the apoptosis-related genes induced by MC-LR in zebrafish liver. The messenger RNA abundance of some apoptosis-related genes was found to be increased, including five tumor necrosis factor (TNF)-related members (apoptosis regulatory protein siva, tumor necrosis factor–α (tnfa) TNF (ligand) superfamily member 10 (tnfsf10), TNF-inducible protein 6 (tnfaip6) and TNF receptor associated factor 2 binding protein (traf2bp)), three p53-related genes (tumor protein p53 inducible nuclear protein 1 (tp53inp1), p53-induced protein phosphatase 1 (ppm1d) and a novel apoptosis stimulating protein of p53 (aspp2)), bcl 2 family members (proapoptosis gene bax and antiapoptosis gene mcl 1), caspases (caspase y (caspy) and a PYD and CARD domain-containing protein (pycard)) and the transforming growth factor beta (TGF-β) induced apoptosis protein 2 (taip2). Real-time polymerase chain reaction was used to study the kinetic transcriptional changes in seven apoptosis-related genes. Elevated transcription of p53, tp53inp1, mcl 1 and taip2 could only be detected at 6 h, increased transcription of the antagonist molecules, bcl 2 and bax could be detected at most time points and the significant change of caspy could be found at 48 h and 72 h after stimulation. Taken together, the results obtained in the present study clearly demonstrate that large amount of apoptosis-related genes are involved in the regulation of MC-LR-induced apoptosis.
The essential oils having many application fields such as medicine, flavoring, cosmetics are natural products obtained from aromatic plants. As the natural products of Ferula species have a wide range of use in folk medicine, this study was planned to evaluate the mutagenic and antimutagenic activities of essential oils of leaves and flowers of Ferula orientalis grown in Erzurum, through the bacterial reverse mutation assay. Furthermore, the chemical compositions of essential oils isolated by the hyrodistillation method were analysed by gas chromatography (GC) and gas chromatography–mass spectroscopy (GC-MS), as their biological activities were connected to their contents. According to our results, any tested essential oil at any used concentration on Salmonella typhimurium TA1535 and TA1537 strains and in Escherichia coli WP2 uvrA strain showed no mutagenic activity. However, the tested materials at different concentrations showed antimutagenic activities against the used mutagens. The inhibition rates ranged against sodium azide (NaN3) on S. typhimurium TA1535 from 29% to 36%, against 9-aminoacridine (9-AA) on S. typhimurium TA1537 from 40% to 68% and against N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) on E. coli WP2 uvrA from 23% to 52%, respectively. Also, it is revealed by GC and GC/MS analysis of the essential oils isolated from the leaves and flowers, respectively. The major compounds in these oils were determined as α-cadinol, -cadinene and germacrene D-4-ol. The results of this study indicate that as the essential oils of F. orientalis have many constituents, they show no mutagenic activity but significant antimutagenic activity, and these materials can be safely used in medicinal applications after further investigations.
The present study has examined the effect of different concentrations (1 μg/ml, 10 μg/ml and 100 μg/ml) of titanium oxide (TiO2) nanoparticles (NPs) (<100 nm) on viability, membrane integrity, capacitation status and DNA integrity of buffalo spermatozoa. Characterization of NPs was done by the transmission electron microscopy (TEM) and dynamic light scattering (DLS). Sperm chromatin dispersion (SCD) test and acridine orange test (AOT) were employed to detect DNA fragmentation in sperm treated with NPs. There was significant (p < 0.05) decrease in cell viability and membrane integrity (assessed by enzyme leakage) at 6 h of incubation with NPs. However, significant (p < 0.05) increase in sperm capacitation was observed for TiO2 NP albeit at lower concentrations. In DNA fragmentation assay, there was dose-dependent increase in the DNA fragmentation (r = 0.96). Ultrathin cross-sections revealed TiO2 NPs inside head and plasma membrane of the buffalo spermatozoa as assessed by TEM. These studies suggest that TiO2 NPs may have cytotoxic effect on buffalo spermatozoa by affecting sperm functionality and causing high amount of DNA fragmentations.
This study aimed to investigate the protective effect of selenium (Se) on methimazole (MMI; an antithyroid drug)-induced hepatotoxicity in adult rats and their progeny. Female Wistar rats were randomly divided into four groups of six rats in each group: group I served as controls that received standard diet; group II received MMI in drinking water as 250 mg L-1 and standard diet; group III received both MMI (250 mg L-1, orally) and Se (0.5 mg kg-1 of diet); group IV received Se (0.5 mg kg-1 of diet) as sodium selenite. Treatments were started from the 14th day of pregnancy until day 14 after delivery. Exposure of rats to MMI promoted oxidative stress with an increase in liver malondialdehyde levels, advanced oxidation protein products and protein carbonyl contents and a decrease in the levels of glutathione, nonprotein thiols and vitamin C. A decrease in the activities of liver glutathione peroxidase, superoxide dismutase, catalase and lactate dehydrogenase and in the levels of plasma total protein and albumin was also observed. Plasma transaminase activities and total, direct and indirect bilirubin levels increased. Coadministration of Se through diet improved all biochemical parameters. The histopathological changes confirmed the biochemical results. Therefore, our investigation revealed that Se, a trace element with antioxidant properties, was effective in preventing MMI-induced liver damage.
In this survey the incidence of aflatoxin M1 (AFM1) contamination in some dairy products collected from the Iran market was investigated using enzyme-linked immunosorbent assay (ELISA) technique. From February 2011 to February 2012, a total of 200 samples composed of yoghurt (60 samples), cheese (80 samples), and ice-cream (60 samples) showed that 75.5% of the tested samples were contaminated with various levels of AFM1 ranging from 14.3 to 572.1 ng/L. AFM1 was detected in 48 (80.0%) yoghurt samples (ranging from 19.7 to 319.4 ng/L), in 69 (86.3%) chesses samples (ranging from 14.3 to 572.1 ng/L) and in 34 (56.7%) of ice cream samples ranging from (ranging from14.9 to 147.4 ng/L). Eleven of cheese samples (13.8%) and three of yoghurt samples (5.0%) were higher that maximum tolerance limit accepted by European union/codex Alimentarius (250 ng/L). It was concluded that widespread occurrence of AFM1 in cheese samples was considered to be possible hazards for public health especially for children. This study suggests a regular monitoring of AFM1 in milk and milk products in the country.
The pathogenicity of enterohemorrhagic Escherichia coli (EHEC) strains is, in large part, due to shiga toxin (Stx) genes (Stx1 and Stx2) and/or intimin (eae) gene. The purpose of this study was to analyze the role of domestic canaries (Serinus canaria domestica) as a reservoir of Stx and intimin producing strains of E. coli. For this study, a total of 50 cloacal swabs were collected from 50 healthy domestic canaries. Cloacal swabs were cultured and tested using standard methods of microbiology. After primary identification of E. coli, DNA was extracted and polymerase chain reaction was performed using specific primers for Stx1, Stx2 and eae genes. In this study, three of 50 samples were found to be Stx2 positive. In the present study, nine (18%) of 50 canaries tested were positive for eae gene. Only 2% of total canaries tested were positive for simultaneous Stx and eae genes. By considering the presence of Stx genes in E. coli isolated from cloacal contents of canary, this hypothesis expressed that the canaries may be the carriers of virulence genes that can risk human health. Canary was considered to be a reservoir of Stx and intimin genes and make these birds important vehicles for the spread of zoonosis infection.
The toxicity of dental materials has raised public concern over the past years. One of the most commonly used methacrylic monomers for building the three-dimensional structure of the dental resin composites is 2,2-bis[4-(acryloxypropoxy)phenyl]propane (BAPP). The purpose of this study is to evaluate the potential toxicological implication of BAPP on human gingival fibroblasts (HGFs). Flow cytometric, fluorometric, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) colorimetric assays were used to detect the mode of cell death, caspase activities, and cell viability, respectively. In addition, alkaline single-cell gel electrophoresis (COMET) and cytokinesis block micronucleus (MN) assays were applied to evaluate the genotoxicity. According to the results BAPP demonstrated a cytotoxic effect on HGFs in a dose- and time-dependent manner. With increasing concentrations of BAPP, the mode of cell death shifted from apoptosis to necrosis, and the activities of caspases 3, 8, and 9 were also significantly induced. Moreover, a dose-related increase in the number of micronucleus and DNA strand breaks hinted at the expression of genotoxicity by BAPP. In conclusion, the results gathered from this study had demonstrated that BAPP-induced cytotoxicity and genotoxicity on HGFs were mediated by DNA damage and the activation of caspases 3, 8, and 9.
The effects of long-term drought stress on chlorophyll, proline, protein and hydrogen peroxide (H2O2) contents, malondialdehyde (MDA) in terms of lipid peroxidation and on the changes in the activities of antioxidant enzymes such as superoxide dismutase (SOD, EC 1.15.1.1), ascorbate peroxidase (APX, EC 1.11.1.11), catalase (CAT, EC 1.11.1.6) and peroxidase (POX; EC 1.11.1.7) in the leaves of pea (Pisum sativum L.) were studied in field conditions. Chlorophyll and protein contents in leaves decreased significantly with increased drought stress. The proline content increased markedly under water deficit. MDA amounts were elevated as a result of water shortage, whereas H2O2 content changed slightly in pea leaves exposed to drought stress. Drought stress markedly enhanced the activities of SOD, CAT and POX but slightly changed the activity of APX. We conclude that in field conditions, long-term water shortage increased the susceptibility to drought in peas.
Arsenicosis caused due to drinking of arsenic contaminated ground water is a major environmental health hazard throughout the world. We evaluated the ecotoxicological effect of arsenic on chicken and duck in an arsenic endemic zone. The concentration of arsenic was higher in chicken and duck feed and their by-products than that in the respective samples of control area. Arsenic concentration in the eggs of both chicken and duck was higher than that in the respective samples of control area. Thus, we concluded that arsenic enters into food chain through the intake of contaminated eggs. Furthermore, adverse health effect of arsenic on avian population is due to the alteration in haematobiochemical indices.
We aimed to assess the effect of exposure to pesticide on platelet indices including mean platelet volume (MPV) and platelet distribution width (PDW) in farm workers. The study group consisted of 40 farm workers (4 females, 36 males; mean age 42.6 ± 9.8 years). An age-, gender- and body mass index–matched control group was composed of 38 healthy volunteers (8 females, 30 males; mean age 46.1±8.9 years). Platelet indices were assessed in farm workers exposed to pesticides. MPV values were significantly lower in farm workers than in those of controls (6.3 ± 1.1 vs. 7.6 ± 0.7 fL, respectively; p < 0.001). Platelet count was significantly lower in farm workers than those of controls (155.7 ± 35.7 vs. 271.3 ± 96.2 x 109/L, respectively; p < 0.001). PDW was significantly lower in farm workers than in those of controls (8.9% ± 2.0% vs. 15.8% ± 0.8%, respectively; p < 0.001). We have found that MPV and other platelet indices were significantly lower in farm workers exposed to pesticides than those of controls. Our findings suggest that MPV may be a sensitive indicator of a pesticide-exposure effect.
The aim of the present study was to find out the potential impact of occupational exposure to mixtures of organic solvents on liver function tests. Serum bile acid (BA) was evaluated as a marker of early hepatic derangement and compared to routine liver function tests. The study included two comparable groups: 57 male workers exposed to organic solvents from a paints factory and 59 administrative male controls. Occupational and medical data and serum analysis for liver function parameters (BAs, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), total and direct bilirubin) were obtained. Bile acids showed significantly elevated mean levels in the exposed workers compared to the controls (50.2 ± 47.9 and 5.4 ± 2.7 µmol/L, respectively, p < 0.01). Bile acids were elevated in almost all exposed workers (87.7%) but in none of the controls. Bile acids had significant positive correlation with duration of exposure to organic solvents and lifetime hydrocarbon exposure score (HES) (p < 0.01 and p < 0.05, respectively). All other liver function tests exhibited normal mean levels and did not show statistically significant differences between both groups. The performance of BA versus combined liver enzymes is evaluated using receiver–operating characteristic (ROC) curve and likelihood ratios. The area under the curve was significantly high (0.687 > 0.5, p = 0.012) and had optimal decision level (8 µmol/L). Serum BA can be recommended as a screening test for exposure to organic solvents. It can be suggested for follow-up every 1–2 years or accordingly.
Cigarette smoke contains harmful chemicals with hazardous adverse effects on almost every organ in the body of smokers as well as of nonsmokers exposed to environmental tobacco smoke (ETS). There has been increasing interest in the effects of passive smoking on the health of children. In order to detect the magnitude of passive smoking in children, parental questionnaires, measuring nicotine and cotinine body levels, and evaluating expired carbon monoxide (CO) concentrations, have been used. Passive smoking causes respiratory illness, asthma, poor growth, neurological disorders, and coronary heart diseases. Herein, we focused on the deleterious influences of passive smoking on immunity and liver. Besides, its effects on the concentrations of various biomarker levels related to the oxidant/antioxidant status were considered. Understanding these effects may help clinicians to counsel parents on smoking cessation and smoke exposure elimination. It may also help to develop interventions to improve the health of children. This review potentially demonstrated some nutraceuticals with a promising role in the prevention of smoking-related diseases.
Thioacetamide (TAA) is a potent hepatotoxin that causes centrilobulal necrosis and nephrotoxic damage following acute administration. Prolonged exposure to TAA can result in bile duct proliferation and liver cirrhosis histologically similar to that caused due to viral hepatitis infection. Coriander in food increases the antioxidant content, acting as a natural antioxidant and inhibiting undesirable oxidation processes. The present study investigated the antioxidant activity of Coriandrum sativum on TAA-induced hepatotoxicity in the male rats. Phenolic content and antioxidant activity were evaluated in the coriander leaves and seeds. Forty-eight adult male rats were divided into four groups. Group I (control), group II (TAA injected rats), group III (TAA injected rats fed coriander leaves) and group IV (TAA injected rats fed coriander seeds). The results revealed that serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities were significantly increased in the groups II, III and IV as compared to the normal control. Oxidative stress in the group II was manifested by a significant rise in nitric oxide (NO), thiobarbituric acid reactive substance (TBARS) levels and myloperoxidase (MPO) activities in the liver tissues as compared with the control group. Rats fed with coriander leaves and seeds showed a decrease in the serum ALT, AST and ALP activities and in the liver NO and TBARS levels as compared to the group II. Histopathological study revealed that coriander feeding attenuated TAA-induced hepatotoxicity in the rats. In conclusion, coriander leaves attenuate hepatotoxicity induced by TAA more than that of seeds due to the higher content of phenolic compounds and antioxidants in the leaves of coriander. Liver of rats intoxicated with TAA exhibited advanced cirrhosis in the form of macronodular and micronodular structure surrounded by fibrous tissue. Treatment with coriander leaves and seeds helps in improving the adverse effect of TAA-induced hepatotoxicity; also the histological study confirms this finding.
In the present study, we attempted to elucidate the induction of autophagy in rat hepatocytes by a low concentration of mercury. Hepatocytes treated with different doses of mercuric chloride (HgCl2; 1, 2.5, 5 and 10 µM) and at different time intervals (0 min, 30 min, 1 h, 2 h and 4 h) show autophagic cell death only at 5 µM HgCl2 within 30 min of incubation. At 1 and 2.5 µM HgCl2, no cell death is recorded, while apoptosis is found at 10 µM HgCl2, as evidenced by the activation of caspase 3. Autophagic cell death is confirmed by the presence of monodansylcadaverine (MDC) positive hepatocytes which is found to be highest at 1 h. Atg5-Atg12 covalent-conjugation triggers the autophagic pathway within 30 min of 5 µM HgCl2 treatment and continues till 4 h of incubation. In addition, damage-regulated autophagy modulator (DRAM) expression gradually increases from 30 min to 4 h of treatment with mercury and a corresponding linear decrease in p53 has been observed. It is concluded that a low concentration (5 µM HgCl2) of mercury induces autophagy or nonapoptotic programmed cell death following an Atg5-Atg12 covalent-conjugation pathway, which is modulated by DRAM in a p53-dependent manner.
Drug dependence is a pattern of repeated self-administration of a drug, which can result in tolerance, withdrawal and compulsive drug-taking behaviour. It has been recently suggested that 5-HTTLPR (LL/LS/SS) variants and rs25531 (A/G) polymorphism in the serotonin transporter gene (SLC6A4) may play a role in drug dependence. The current study aimed to (1) identify allelic, haplotypic and genotypic frequencies of the 5-HTTLPR variants and rs25531 polymorphisms of SLC6A4 gene in drug and nondrug-dependent Jordanian Arab population and (2) determine whether there is an association of these variants in a drug-dependent population from the same area. Jordanian drug male addicts of Arab descent (n = 192) meeting the Diagnostic and Statistical Manual of Mental Disorders – Fourth edition criteria for drug dependence and 230 healthy male controls from an ethnically homogenous Jordanian Arab population were examined. Genotyping was performed using the restriction fragment length polymorphism–polymerase chain reaction-based method to genotype the 5-HTTLPR variants and detect the A/G polymorphism at position rs25531. The biallelic analysis revealed that the frequency of 5-HTTLPR (LL/LS/SS) genotypes was statistically significant different between drug-dependent individuals and controls (2 (2, N = 422), p = 0.04). Drug-dependent subjects had a higher frequency of ‘L’ allele. However, using the triallelic approach, the estimated frequency of haplotypes (SA, SG, LA and LG) and phased genotypes (LA/LA, LA/SA, LA/LG, SA/SA and SA/SG) did not show significant association with drug dependence (2 (3, N = 422), p = 0.53 and 2 (4, N = 422), p = 0.06, respectively). This study suggests a putative role of the 5-HTTLPR for drug dependence in the Jordanian Nationals of Arab ancestry.
Flavonoids are group of compounds that have been shown to possess potent anti-inflammatory effects in both cellular and animal models of inflammation. In the current study, the single and combined effects of the two flavonoids, curcumin and quercetin, against carrageenan-induced acute inflammation in rats were evaluated with emphasis on the role of oxidative stress, anti-inflammatory enzyme, heme oxygenase-1 (HO-1) and proinflammatory cytokine, tumor necrosis factor-alpha (TNF-α). Curcumin (50 mg/kg), quercetin (50 mg/kg) and a combination of both were orally administered for 14 days before carrageenan injection in rats and compared with the reference nonsteroidal anti-inflammatory drug, indomethacin (10 mg/kg). The percentage increase in paw thickness was calculated. Frozen hind paws were used for the estimation of lipid peroxides (malondialdehyde, MDA), nitric oxide (NO), reduced glutathione (GSH), TNF-α level and HO-1 messenger RNA (mRNA) expression. Formalin-fixed hind paws were used for histopathological examination. Results showed that both curcumin and quercetin caused reduction in carrageenin-induced edema and lymphocytes infiltration along with the decrease is being even higher in case of their combination. Additionally, both flavonoids reduced MDA and NO formation, and restored GSH contents in the paw. Furthermore, both flavonoids increased HO-1 mRNA expression and decreased the elevated TNF-α level. Results showed that both flavonoids moderately lowered inflammation, while their combination was more effective. Accordingly, this study suggests that the reduction in oxidative stress and modulation of HO-1 mRNA expression and TNF-α release by curcumin and quercetin may contribute to the synergistic anti-inflammatory effects of these two flavonoids upon combination.
Mancozeb is a fungicide belonging to the ethylene-bisdithiocarbamate group and is widely used in agriculture. The aim of this study was to examine the protective effect of quercetin (QRN) against oxidative stress induced by mancozeb in human erythrocytes. In order to verify this, 5 ml of venous blood was collected and the erythrocytes were separated and divided into equal parts. One part was incubated with different concentrations of mancozeb (0, 10, 30, 100 µM) for 4 h at 37°C. The other part was preincubated with QRN (40 and 80 μM) for 30 min, followed by mancozeb (0, 10, 30, 100 µM) incubation for 4 h. We found reduction in the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione (GSH) along with elevated levels of lipid peroxide (LPO) in erythrocytes incubated with 30 and 100 µm of mancozeb. Pre-incubation with QRN (80 μM) reversed oxidative stress induced by mancozeb (30 μM) and inhibited LPO induced at 100 μM by 64.36%. QRN also reduced the haemolytic effect on erythrocytes but could not prevent the induction of haemolysis by mancozeb. Therefore, these results suggest that QRN may play a role in preventing the oxidative stress induced by mancozeb in human erythrocytes.
Cyclophosphamide (CP) is an alkylating agent that has been considered effective for cancer treatment. Lycopene, the pigment in tomato fruits, has beneficial effect in the treatment of some diseases. The goal of this study is to evaluate the protective effect of lycopene alone or combined with melatonin (Mel) in inhibiting the oxidative stress and toxic effect of CP in rats. Five groups of rats were included in this study; Group I served as the control. Rats in groups II-V were administrated with single dose of CP (150 mg/kg B.W) interperitoneally for 3 days. On the same day of CP administration, the rats in group III were fed a diet supplemented with lycopene (50 mg/kg of diet), rats in group IV were administered with a dose of 2.5 mg Mel/kg body weight (bw) injected subcutaneously and rats in group V were supplemented with lycopene and a dose of 2.5 mg Mel/kg bw injected subcutaneously. After 15 days the blood samples were collected. Results obtained showed that CP exerted its toxic effect by increasing the free radicals and reactive oxygen species that causes lipid peroxidation and cell damage, and this in turn is detected by elevation in nitric oxide (NO) and malondialdehyde (MDA), while the activities of antioxidants enzymes including (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)) were significantly decreased as compared with the control rats. The combined treatment (Lyco + Mel) group showed potential reduction in these parameters more than those treated with lyco alone. The activities of SOD, CAT and GPx were found significantly high than lyco alone treated rats. A positive significant correlation between NO and MDA (r = .81). In conclusion, these results suggested that supplementation of diet with lycopene and Mel provided antioxidant defense with strong chemopreventive activity against Cp-induced cytotoxicity.
Quercetin (3,5,7,3',4'-pentahydroxy flavone) is a potent antioxidant found in various fruits and vegetables. The present investigation was an attempt to evaluate the mitigatory effect of quercetin on the damage caused by bisphenol A (BPA; 2,2-bis (4-hydroxyphenyl) propane), a well-known xenoestrogen, on liver and kidney of mice. Swiss strain adult male albino mice were orally administered with 120 and 240 mg/kg body weight (bw)/day BPA with or without quercetin (60 mg/kg bw/day) for 30 days. On the completion of the treatment period, animals were killed; organs were isolated and used for the study. Results revealed that oral administration of BPA for 30 days caused significant and dose-dependent decrease in body weight. Absolute and relative organ weights, total lipid and cholesterol contents were significantly increased in liver and kidney of mice when compared with vehicle control. BPA treatment also caused, when compared with vehicle control, a statistically significant reductions in the activities of catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase as well as in glutathione and total ascorbic acid contents; however, significant increase was found in malondialdehyde (MDA) levels. Histopathological studies revealed hepatocellular necrosis, cytoplasmic vacuolization and decrease in hepatocellular compactness in liver as well as distortion of the tubules, increased vacuolization, necrosis and disorganization of glomerulus in the kidney of BPA-treated mice. All these effects were dose-dependent. Co-treatment with quercetin (60 mg/kg bw) and BPA (low dose and high dose) alleviates the changes in body weight, as well as absolute and relative organ weights of mice. It also ameliorates the oxidative stress created by BPA by lowering MDA levels and by increasing enzymatic and nonenzymatic antioxidants as well as it brings back the normal histoarchitecture of liver and kidney of mice. The present results revealed that graded doses of BPA caused oxidative damage in liver and kidney of mice, which is mitigated by quercetin.
Rice (Oryza sativa Linn) is one of the basic diets in the north of Iran. The aim of present study was to detect total aflatoxin (AFT) in domestic and imported rice in Amol (in the north of Iran) and to evaluate the effect of different cooking methods on the levels of the toxin. For this purpose, 42 rice samples were collected from retail stores. The raw samples were analysed by enzyme-linked immunosorbent assay (ELISA) technique for toxin assessment and then submitted to two different cooking methods including traditional local method and in rice cooker. After treatment, AFT was determined. Results show that the average concentration of AFT in domestic and imported samples was 1.08 ± 0.02 and 1.89 ± 0.87 ppb, respectively, which is lower than national and European Union standards. The highest AFT reduction (24.8%) was observed when rice samples were cooked by rice cooker but the difference with local method was not statistically significant (p > 0.05).
Nanotechnology is a major scientific and economic growth area and presents a variety of hazards for human health and environment. It is widely believed that engineered nanomaterials will be increasingly used in biomedical applications (as therapeutics and as diagnostic tools). However, before these novel materials can be safely applied in a clinical setting, their toxicity needs to be carefully assessed. Nanoscale materials often behave different from the materials with a larger structure, even when the basic material is same. Many mammals get exposed to these nanomaterials, which can reach almost every cell of the mammalian body, causing the cells to respond against nanoparticles (NPs) resulting in cytotoxicity and/or genotoxicity. The important key to understand the toxicity of nanomaterials is that their minute size, smaller than cellular organelles, allows them to penetrate the basic biological structures, disrupting their normal function. There is a wealth of evidence for the noxious and harmful effects of engineered NPs as well as other nanomaterials. The rapid commercialization of nanotechnology field requires thoughtful, attentive environmental, animal and human health safety research and should be an open discussion for broader societal impacts and urgent toxicological oversight action. While ‘nanotoxicity’ is a relatively new concept to science, this comprehensive review focuses on the nanomaterials exposure through the skin, respiratory tract, and gastrointestinal tract and their mechanism of toxicity and effect on various organs of the body.
Water-soluble carbon nanotubes have been found to be one of the most promising nanomaterials in biological- and biomedical-based applications. However, there have been major concerns on their ability to cause cellular and DNA damages upon exposure. In this work, we explore the toxic effects of three multiwalled carbon nanotubes (MWCNTs: nonpurified, purified and carboxylate-functionalized) on human skin keratinocytes (HaCaT). Cytotoxicity tests using the conventional thiazolyl blue tetrazolium bromide (MTT) and the water-soluble tetrazolium (WST-1) assays for 0.5 or 24 h exposure to 20 μg/mL of MWCNTs show that all three caused minimum cytotoxicity that is generally not statistically significant. Assessment of direct and oxidative DNA damages using both alkaline Comet assay and formamidopyrimidine DNA glycosylase-modified Comet assay reveals that the treatment with 20 μg/mL of MWCNTs does not cause significant direct DNA damages, but causes great amount of oxidative DNA damages in HaCaT cells. The oxidative DNA damage reaches the maximum amount at 4 h of incubation in Dulbecco’s minimum essential medium, but decreases to the minimum at 8 and 24 h of incubation, indicating repair of the oxidative damages by the intrinsic DNA repair mechanism of the cells.
The contamination of apple juice with patulin mycotoxin is a major risk factor in food safety. This study focuses to assess the biochemical and histopathological effects of patulin in apple juice samples collected from different outlets retailing in Jeddah, Kingdom of Saudi Arabia. On the basis of the selected dose level, 152.5 ppb patulin/ml was administered daily orally for up to 6 weeks to male albino mice. The exposure to contaminated samples revealed significant elevation of all the studied blood parameters (alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activities as well as creatinine, urea and uric acid contents). On the other hand, and with regard to the accumulated neuronal toxicity of the tested dose level, the toxic signs were recorded as significant increase in the aggressive and locomotor behavioral changes. In addition, the brain areas monoamines concentration revealed variable increased changes. The potential maximal changes in norepinephrine, dopamine and serotonin5-hydroxytryptamine levels attained in cortex, hypothalamus, striatum, hippocampus, midbrain and pons and medulla were assessed. Moreover, the histological examination revealed degeneration and necrosis in liver tissues and degenerated glomeruli and hemorrhage between the tubules of the cortical region in kidney tissues. The study declared that patulin-contaminated (152.5 ppb) apple juice exhibited liver, kidney and neurotoxicological effects in 6 weeks orally administered mice.
Water-soluble binary and ternary copper complexes of polyelectrolytes were synthesized, and the toxicity of these complexes was tested in mouse fibroblast cell line (L929) in vitro. Both the binary and ternary complexes were prepared at the ratio of 0.4 mole copper(II) ions per monomer of acrylic acid and 0.5 mole copper(II) ions per monomer of methyl vinyl ether maleic anhydride, furthermore at the ratio of 1 and 2 mole bovine serum albumin per mole of polyacrylic acid and poly(methyl vinyl ether-co-maleic anhydride), respectively. Compared to binary copper(II)–polyelectrolyte complexes, these ternary complexes have been determined to be of least toxicity.
The present study was conducted to investigate the potential role of 2,4-dichlorophenoxyacetic acid (2,4-D) in inducing developmental toxicity and oxidative damage in pregnant rats and their fetuses as well as to assess the efficacy of vitamin E to prevent or alleviate such defects. Pregnant rats received 2,4-D (100 mg/kg bw) alone or in combination with vitamin E (100 mg/kg bw) daily from gestation day 1 to 19. The number of implantations, viable and resorbed fetuses and sex ratio were not statistically different among groups. However, fetuses maternally treated with 2,4-D were characterized by lower body weight and higher morphologic and skeletal defect rate. 2,4-D induced oxidative stress in the liver of mothers and fetuses which was indicated by a significant elevation of malondialdehyde level with reduction in catalase activity and total antioxidant capacity. Coadministration of vitamin E can counteract the deleterious effects of 2,4-D by successive reduction in the oxidative stress.
The objective of this inhalation study was to determine and evaluate the potential toxic effects of dicyclopentadiene vapor in mice exposed for 13-weeks of repeated inhalation. Four groups, each consisting of 45 male and 45 female B6C3F1 mice, were exposed to dicyclopentadiene vapor by inhalation 6 h/day, 5 days/week, for 13 weeks (64 exposures) at targeted concentrations of 0, 1.0, 5.0, or 50 ppm. An assessment of toxicity is carried out after 2, 6, and 13 weeks of inhalation exposures. Additionally, animals were evaluated during the recovery period of 4 or 13 weeks after the last exposure. Observations and measurements to assess toxicity include clinical observations, body weight, organ weights, serum chemistry, and hematologic, ophthalmologic, gross pathologic, and histologic evaluations. The only systemic effects observed were a few statistically significant changes in organ weights; but these were considered spurious in nature. Ten male and nine female mice in the highest exposure group died during the study, while no more than two mice died in any other group. However, the excess mortality was without an apparent etiology or association to exposure and was attributed to pulmonary congestion as a consequence of pulmonary irritation. Under the conditions of this study, these data demonstrated that in the absence of overt systemic toxicity, respiratory congestion has the predominant effect at the exposure levels of 50 ppm. This observation contributes to the Globally Harmonized System harmonized hazard classification of Single Target Organ Toxicity – Single Exposure (H335, may cause respiratory irritation) for this substance.
The endotoxin, lipopolysaccharide (LPS), of Salmonella typhimurium was biosynthetically labeled with 3H and 14C incorporated into the fatty acyl chains and glucosamine residues, respectively. The radio-labeled LPS was isolated from the bacteria and then injected into Sprague-Dawley rats. The distribution of 14C and 3H-LPS in plasma and other organs was determined following intraperitoneal (IP) doses of 14C and 3H-LPS (200 μg/kg). Plasma concentrations of both fatty acyl chains and glucosamine residues were biphasic, with a relatively rapid decay followed by a slow decline for 48 h. Similar biphasic results were found in the peripheral organs (kidney and heart) and brain barrier tissues (meninges and choroid plexus). In other brain tissues (brain stem, caudate nucleus, hypothalamus, frontal cortex, cerebellum and hippocampus), the glucosamine residue was biphasic, whereas the fatty acyl chains showed accumulation. Highest concentrations of LPS were found in the plasma, spleen and the liver. In addition, in the liver, sustained elevations of 14C-glucosamine and 3H-fatty acyl chains were observed. This indicates LPS accumulation in the liver. By contrast, the spleen showed biphasic decay of glucosamine residues and accumulation of fatty acyl chains. In the brain barrier tissues, peak LPS concentrations were significantly reduced (about 70%) and were further reduced (about 95%) in other brain tissues. The high elevation of LPS in the spleen is considered indicative of an immune response. Our findings highlight the potential significant role of lipid A as shown with the sustained elevation of 3H-fatty acyl chains in the brain.
We have previously measured the distribution and pharmacokinetics of biosynthetically radiolabeled endotoxin of Salmonella typhimurium following intraperitoneal (IP) dosing (200 μg/kg) in Sprague-Dawley rats. In our experiments, the fatty acid residues were labeled with 3H and the glucosamine residues were labeled with 14C. To predict the dynamics of endotoxin exposure, we developed a physiological-based pharmacokinetic model using our measured distribution results. The model was validated with published low-dose (30 μg/kg) IP exposure results in rats. Endotoxin pharmacokinetics depended on dose and route. At high IP doses, absorption was followed by biphasic decay over 48 h in plasma. There were tissue accumulations of the fatty acid and glucosamine residues in various target organs, including the brain. We also found that the glucosamine and fatty acid components separated in vivo about 3 h after IP injection. At the lower IP dose, a smaller fraction of the dose was distributed to the tissues, with most of the dose remaining in the blood. Each component had its own dynamic behavior and target tissue distribution in the rat. The fatty acid components tended to remain in the brain stem, caudate nucleus, cerebellum, frontal cortex, hippocampus, and hypothalamus. Other organs (spleen, kidney, meninges, and choroid plexus) had similar biphasic distribution. The liver had the unique accumulation of both glucosamine and fatty acid residues.
Although higher protein yield per hectare of water hyacinth than that of soy, high protein content of its leaves and good essential amino acid pattern have been proven, its dietary toxicity for human or animal consumption has not yet been evaluated. Therefore, the acute toxicity of water hyacinth leaves has been evaluated by an animal feeding test. The concentrations of common toxic metals including cadmium, lead, platinum, palladium, tin, mercury, barium, silver, stibium and aluminum in the water hyacinth leaf powder (WHLP) used for the animal feeding test were within their maximum limits in food additives as reported by the World Health Organization. The median lethal dose (LD50) of WHLP was more than 16 g kg-1 body weight. In the study, after feeding for 7 and 28 days, the body weight of all the mice increased. The results of hematological analysis, clinical biochemical analysis, histopathological evaluation, general dissection or investigations of internal organs, appearance and behavior observations did not indicate any adverse effects from the diet containing WHLP. It is therefore concluded that water hyacinth leaves are not acutely toxic.
Sodium 3,5,6-trichloropyridin-2-ol (STCP) is an important intermediate for synthesizing organophosphate insecticide chlorpyrifos. At present, chlorpyrifos is one of the world’s largest species of pesticide products. Many studies have focused on the toxicity of chlorpyrifos, but few reports have looked at the toxicity mechanism of STCP. Even fewer studies have looked at STCP poisoning. With increasing production and usage of STCP, the chances of such poisoning will increase. In this study, we present a report on four workers who helped in the industrial manufacture of STCP and who were affected by exposure to it. We hope that these case studies will provide a foundation for further research into STCP.
This study was designed to investigate whether extracorporeal shock wave lithotripsy (ESWL) exposure to parotid gland produces an oxidative stress in parotid glands of rats. Twelve male Wistar-albino rats, 6 months of age with an average body weight of 250–300 g, were divided randomly into two groups, each consisting of six rats. The animals in the first group did not receive any treatment and served as control. The left parotid glands of animals in group 2 (ESWL treated) received a thousand 18 kV shock waves after anesthetizing the rats with 50 mg/kg of ketamine. The animals in both groups were killed 72 hours after the ESWL treatment, and the parotid glands were harvested for the determination of lipid peroxidation product malondialdehyde (MDA), antioxidant glutathione (GSH) levels and the activities of antioxidant enzymes such as superoxide dismutase (SOD), GSH-Px and catalase (CAT). It was found that MDA level increased in parotid glands of rats after the ESWL treatment. The SOD, GSH-Px and CAT enzyme activities, and the level of antioxidant GSH decreased in parotid gland of rats after the ESWL treatment. It was concluded that short-term ESWL treatment caused an increase in the free radical production and a decrease in the antioxidant enzyme activity in parotid glands of ESWL-treated rats.
N, N, N', N'-tetramethylethylenediamine (TEMED) is extensively used for initiating polymerization of acrylamide and bisacrylamide gel for electrophoresis and for inorganic complex structure formation. The present study evaluates the toxicological effect of TEMED on structures of rat brain acetylcholinesterase (AChE) activity. In vitro study showed that the Ki values for striatum, cortex, cerebellum and hypothalamus were found to be 1.24, 1.4, 1.45 and 1.47 mM. Kinetics studies indicated that TEMED caused mixed type of inhibition that is a combination of competitive and noncompetitive inhibition in striatum, cortex, hypothalamus and cerebellum. The result showed that km increased and Vmax decreased with increase in TEMED concentration. The IC50 values calculated for striatum, cortex, cerebellum and hypothalamus were found to be as 0.92, 0.92, 1.44 and 1.42 mM. The present study indicates that TEMED is a toxicant for brain via inhibition of AChE. Therefore, proper precaution should be made during its handling.
A short-term in vivo genotoxicity evaluation of 4-carboxyl-2,6-dinitrophenylazohydronaphthalenes (AZ-01 to AZ-04) has been carried out in mice. Aqueous colloidal solutions of the dyes were administered to mice on each day for 5 successive days using gastric gavages. Two end point assessments of the genotoxicity potentials of the dyes were assessed using comet assay and chromosomal aberration studies using the mice bone marrow cells. The dyes were well tolerated at the doses investigated, as there were no deaths or any adverse pharmacotoxic events. Dose-dependent DNA damage (in terms of percentage of tail DNA and Olive tail moment) occurred with AZ-01 and AZ-02, although the effects were significant only with the highest doses. AZ-03 gave similar patterns with those of AZ-01 and AZ-02, while replacement with butanone in AZ-04 altered the observed pattern. Minimal chromosomal damages were obtained for the four dyes, with AZ-01 and AZ-02 giving nonsignificant damages, while the highest dose of AZ-03 produced significant aberrations in terms of breaks. Some minor isochromatid breaks and gaps were also noticed in the dye-treated mice. Mitotic indices in all cases were not significantly different from concomitantly administered vehicle control showing lack of cytotoxicity of the monoazo dyes at these doses. The monoazo dyes show the potential of being utilized as colorants, pending further required tests.
The present work is an attempt to elucidate the antiulcer activity of indole-3-carbinol (I3C), which is one of the anticarcinogenic phytochemicals found in the vegetables of Cruciferae family such as broccoli and cauliflower, alone or in combination with omeprazole (OMP), a proton pump inhibitor, to diminish the effects of induced acute gastric ulcer by aspirin (ASA) in male albino rats. A total of 48 adult male albino rats were used in the present study. Animals were divided into eight experimental groups (six animals each group). They were given different experimental inductions of ASA at a dose of 500 mg/kg/body weight, OMP at a dose of 20 mg/kg/body weight and I3C at a dose of 20 mg/kg/body weight either alone or in combination with each other orally for a duration of 7 days. Inner stomach features, ulcer index, pH activity, body weight, stomach weight, hematological investigations, serum total protein albumin and reduced glutathione activity were investigated in addition to the histological, histochemical and immunohistochemical stain of cyclooxygenase-2 to the stomach tissue of normal control, ulcerated and treated ulcerated rats. The results of this study revealed that oral administration of ASA to rats produced the expected characteristic mucosal lesions. OMP accelerated ulcer healing but the administration of I3C either alone or in combination with OMP to ASA-ulcerated rats produced a profound protection to the gastric mucosa from injury induced by ASA. Our results suggested that administration of antiulcer natural substances such as I3C in combination with the perused treatment such as OMP is a very important initiative in the development of new strategies in ulcer healing.
The present study was carried out to evaluate the in vitro antioxidant properties and protective effect of lutein in human erythrocyte against benzo(a)pyrene (B(a)P). It is a well-known environmental carcinogen that produces free radicals under normal metabolic circumstances. B(a)P reacts with cellular macromolecules and produces oxidation of protein, lipid and DNA. Lutein is a carotenoid possessing antioxidant, anticarcinogenic and anti-inflammatory properties. In the present investigation, the protective effect of lutein was assessed in vitro against B(a)P-induced oxidative stress by monitoring antioxidant enzymes, lipid peroxidation (LPO), protein carbonyl content, total sulfhydryl (SH) and nonprotein SH groups and methemoglobin in five groups of erythrocytes that include (i) control group, (ii) vehicle control group, (iii) B(a)P-exposed group, (iv) lutein-exposed group and (v) B(a)P coincubation with lutein group. It was observed that the activities of antioxidant enzymes and SH groups were significantly decreased in B(a)P-treated group when compared with control group. LPO level and protein carbonyl and methemoglobin contents were increased in B(a)P-treated group when compared with control group. The erythrocyte that was coincubated with B(a)P and lutein showed significant increase in the antioxidant enzyme activities and a significant reduction in the level of LPO, methemoglobin and protein carbonyl contents when compared with B(a)P-treated group. The results of the present investigation suggest that lutein possess protective effect against B(a)P-induced oxidative stress, possibly by combating oxidative stress by its free radical scavenging activity.
In this study, two sulfonylureas—glimepiride and glipizide—commonly used in type 2 diabetes mellitus were investigated for genotoxicity in the Drosophila wing spot test. For this purpose, three-day-old transheterozygous larvae were treated with three mutagenic compounds, and the results obtained were compared with the control group. Mutational or recombinogenic changes were recorded in two recessive genes—multiple wing hairs (mwh) and flare (flr3). Two recessive markers were located on the left arm of chromosome 3, mwh in map position 0.3, and flare-3 (flr3) at 38.8, while the centromere was located in position 47.7. Wing spot tests are targeted on the loss of heterozygosity, which may be grounded in different genetic mechanisms such as mutation, mitotic recombination, deletion, half-translocation, chromosome loss, or nondisjunction. Genetic changes formatting in somatic cells of the imaginal discs cause nascence different mutant cloning in different body parts of adult flies. Our in vivo experiments demonstrated that glimepiride and glipizide show the genotoxicity, which is especially dependent on homologous somatic recombination.
Objectives: Various authors who studied the effects of aluminium (Al) exposure on the neurocognitive system in the last 30 years have reached different and often contradictory conclusions. The aim of this study is to help clarify the effects that the metal causes on cognitive ability in a group of naval welders exposed to Al.
Methods: The study was performed on a sample of 86 male Al welders in a shipyard in Messina. The average value of environmental Al, recorded in the workplace, was 19.5 mg/m3. The blood levels of Al, zinc, manganese, lead and chromium were monitored in all the subjects. The reagents used for the neuropsychic study were the Wechsler Memory Scale (WMS), the Colour Word Test or Stroop Test and the Test of Attention Matrixes. The results were compared with those obtained in a similar control group not exposed to Al and with an Al-b value of 6.93 g/l.
Results: For all the mental reagents used, the reply is obtained in the sample of exposed subjects showed decreased cognitive response with regard to attention and memory performance. The comparison between the individual tests showed greater sensitivity of performance studied using the WMS and the Stroop Test compared with the Test of Attention Matrixes. The alterations encountered in the cognitive functions studied increased proportionally to time of exposure and quantity of metal absorbed.
Conclusion: The study confirmed that occupational exposure to Al causes alteration in cognitive responses that are more evident in complex functions.
The present study was undertaken to investigate the protective effect of Pleurotus florida lectin (PFL) against arsenic-induced cytotoxicity and oxidative damages in freshly isolated splenocytes of rodents. Our finding indicated that arsenic caused reduction in cell adhesion, morphological alterations, cell proliferation, nitro blue tetrazolium (NBT) index, superoxide dismutase (SOD) activity, catalase (CAT) activity and relative mRNA expression of SOD2 in relation to housekeeping gene glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and increased production of nitric oxide (NO), protein carbonyl (PC) and lipid peroxidation levels (LPO) assembled to play key factors for cytotoxicity and oxidative stress. PFL normalized cellular damages and enhanced SOD production pathway relating to gene expression. Further studies are needed to address effective phytochemicals of the edible mushroom and their mechanism.
Tributyltin (TBT), a well known endocrine disruptor, has high teratogenicity to embryos of amphibian (Xenopus tropicalis). An amphibian metamorphosis assay (AMA) and a complete AMA (CAMA) were conducted for TBT. In AMA, the body weight, the snout-to-vent length and the hind limb length of X. laevis tadpoles were decreased in tributyltin chloride (TBTCl; 12.5–200 ng/L) treatment groups after 7 days exposure. TBT greatly retarded the development of tadpoles, decreased the number of follicle and induced thyroid follicle cell hyperplasia after 19 days exposure. In CAMA, 10 and 100 ng/L TBTCl led to various malformations of gonad, including intersex, segmental aplasia and multiple ovary cavities of X. laevis following exposure from stages 46 to stage 66. The sex ratio was male-biased in TBT treatment groups. These results suggest that TBT delayed the metamorphosis, inhibited the growth of tadpoles and disrupted the gonadal differentiation of X. laevis at environmentally relevant concentrations.
Sulfur dioxide (SO2), which is used as food preservative in apricot sulfurization and several fabricated foods, is a common air pollutant. The aim of this study was to reveal the possible genotoxic effects of SO2 using in vitro human lymphocytes. The different endpoints of genotoxicity: sister chromatid exchange (SCE), micronuclei (MN) tests and cell growth kinetics such as mitotic index (MI) and replication index (RI) were studied. The cells were treated with 0.1, 0.5 and 1.0 ppm concentrations of SO2. It was shown that SO2 caused significant increases in the frequency of SCE and MN in the middle and high dosage groups and also induced mitotic delays and decreased MI and RI. In conclusion, the results have confirmed that SO2 has potent mutagenicity and it can cause genetic damage leading to a malignancy.
Infection of stored wheat flour with insects and toxic fungi can be an extremely serious problem. This study was conducted to isolate and identify the fungal species and insects in different stages, which infested and contaminated the stored flour under Jazan region conditions and changed its color and flavor. The obtained results revealed that the isolated insect was the red flour beetle Tribolium castaneum. Live adult, larvae and cast skin were isolated. Four Aspergillus species were isolated from stored wheat flour; the isolated species prevalence being A. flavus > A. niveus > A. terreus > A. niger by rate 44.5%, 37.8%, 10.9% and 6.7%, respectively. The same fungal species isolated from flour were also isolated from different insect stages. A. flavus was the most common fungus and A. niger was isolated with a lower rate. The results about the isolated fungi either from the suspension of adult insects, larvae or cast skins may confirm the role of T. castaneum to carry and distribute fungi in different parts of the stored flour.
The effects of nitric oxide (NO) on chilling tolerance (contents of hydrogen peroxide (H2O2) and superoxide anion (O2–) and lipid peroxidation level (malondialdehyde, MDA)) and the activities of antioxidant enzymes (superoxide dismutase (SOD), peroxidase (POX) and catalase (CAT)) were investigated in the leaves of wheat (Triticum aestivum L.) exposed to chilling. NO treatment was carried out through spraying of sodium nitroprusside (SNP), which is a donor of NO. To do this, SNP concentrations of 0.1 and 1 mM were applied on the leaves of 11-day plants and the plants were then exposed to chilling conditions (5/2°C) for 3 days. The chilling stress treatment increased both the activities of antioxidant enzymes and the levels of MDA, H2O2 and O2–. Similarly, NO treatment enhanced SOD, POX and CAT activities under chilling stress, whereas it decreased H2O2 and O2.– contents as well as MDA level. The most effective concentration was determined as 0.1 mM SNP. Exogenous SNP application as a donor of NO was found to have an important ameliorative effect on cold tolerance of seedling exposed to chilling stress by stimulating antioxidant enzyme activity.
Arsenic is ubiquitously found metalloid that commonly contaminates drinking water and agricultural food. To minimise the ecotoxicological effect of arsenic in the environment, it is important to ameliorate the deleterious effects on human and animal health. We investigated the effects of arsenic on cattle by estimating arsenic concentration in biological samples of cattle that consumed contaminated drinking water and feedstuffs directly or indirectly. We have selected arsenic prone village that is Ghentugachi, Nadia district, West Bengal, India, along with arsenic safe control village, Akna in Hoogli district, West Bengal, India. It is found that arsenic is deposited highly in blood, urine and faeces. Agricultural field is contaminated through cattle urine, hair, faeces, cow dung cakes and farmyard manure. Bioconcentration factor and biotransfer factor are two important biomarkers to assess the subclinical toxicity in cattle, as they do not exhibit clinical manifestation like human beings.
The current study aims to determine the genotoxic and antigenotoxic potential of four newly synthesized dihydropyridine derivatives using Escherichia coli WP2 and Ames/Salmonella bacterial reversion assay systems. The bacterial mutant tester strains, E. coli WP2uvrA with a point mutation and Salmonella typhimurium TA1537 with a frameshift mutation, were used to determine genotoxic potentials of the test compounds. To determine antigenotoxic potentials of the test compounds, the same strains were also used together with positive mutagens N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for E. coli WP2uvrA and 9-aminoacridine (9-AA) for S. typhimurium TA1537. According to the results, neither of the test compounds showed significant genotoxic activity on both tester strains at the tested concentrations. However, except compound 4, all the test compounds showed significant antigenotoxic activity on MNNG- or/and 9-AA-induced mutations. The inhibition rates of mutagenesis ranged from 27.0% (compound 2: 2.5 mM/plate) to 65.0% (compound 2: 0.5 mM/plate) for MNNG and from 30.6% (compound 2: 2 mM/plate) to 58.5% (compound 1: 1 mM/plate) for 9-AA genotoxicity. According to these results, it is concluded that all the test compounds do not have a mutagenic potential on the bacterial strains at the tested concentrations, and some of them have antigenotoxic potentials against MNNG- and 9-AA-induced mutagenesis.
The aim of the present study was to investigate the effect of atrazine (6-chloro-N2-ethyl-N4-isopropyl-1,3,5-triazine-2,4-diamine) on the left ventricle myocardium in juvenile/peripubertal male Wistar rats. Atrazine was administered orally at 50 or 200 mg/kg of body weight dose for 28 consecutive days. In order to assess possible structural alterations, tissue sections were examined histologically and then subjected to quantification analysis using stereological methods. The tissue specimens were routinely processed and stained with Mallory trichrome method in order to clearly distinguish muscle cells from the connective tissue components. A toluidine blue staining method was additionally used for the demonstration of mast cells. Statistically significant increase in length density and numerical density of capillaries were found at both the investigated doses of atrazine compared with the control. The increase in surface density and volume density of capillaries found at lower dosage of atrazine was significant in comparison with the control. The extensive mast cell degranulation was noted on the histological examination at both doses of the applied chemical. No significant changes were demonstrated for the stereological parameters of cardiomyocytes. Based on the available published data and the present results, it can be concluded that atrazine promoted angiogenesis in the rat myocardium, which might be partially mediated by mast cells.
Carbendazim is a broad spectrum carbamate fungicide used in the control of various fungal pathogens. Licorice (Glycyrrhiza glabra) is one of the widely used medicinal plants in oriental nations. The present work studied the effect of licorice aqueous extract on carbendazim-induced testicular toxicity in albino rats. Administration of carbendazim induced significant decrease in testis weight, diameter, and germinal epithelial height of the seminiferous tubules. Histological results revealed degeneration of seminiferous tubules, loss of spermatogenic cells, and apoptosis. Moreover, carbendazim caused elevation of testicular malondialdehyde (MDA), marker of lipid peroxidation, and reduced the activity of the antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT). Coadministration of licorice extract with carbendazim improved the histomorphological and histopathological changes observed in animals treated with carbendazim. In addition, licorice treatment leads to a significant decrease in the level of MDA and increase in the activities of SOD and CAT. According to the present results, it is concluded that licorice aqueous extract can improve the testicular toxicity of carbendazim and this effect may be attributed to antioxidant properties of one or more of its constituents.
One of the useful and most commonly cultivated commercially species, migratory locust (Locusta migratoria; Orthoptera), was investigated in light of genotoxic damage potentials. For this aim, we evaluated the genotoxic potentials of water soluble extracts of L. migratoria on cultured human blood cells. The micronucleus, sister chromatid exchange and structural chromosome aberration assays were applied to assess DNA and chromosomal damage produced by aqueous extracts in vitro. The extracts were added to the cultures at different concentrations ranging from 0 to 1000 mg/L. Our results indicated that these extracts did not exhibit genotoxicity at tested concentrations. We conclude that this in vitro approach for biomonitoring genotoxicity assessment is useful for comparing the potential health risks of edible insects.
Toxicity of heavy metal is a wide spread environmental problem affecting all life forms including plants. In the present study the toxic effects of heavy metals, cadmium (Cd), chromium (Cr) and lead (Pb) on seed germination rate (%), germination index (G-index) and growth (mm) of Brassica rapa var. turnip have been investigated. The seeds were soaked either in distilled water (control) or in aqueous solutions of Cd, Cr and Pb (1 g/l, 2.5 g/l and 5 g/l) at 4°C in dark for 24 hours. Prior to inoculation onto MS0 medium, the soaked seeds were either washed with sterile distilled water or inoculated without washing on solidified MS0 medium at 25 ± 2°C with 16/8-hour photoperiod in a growth chamber to germinate in vitro. Such stress conditions revealed that by increasing the concentration of heavy metals, the germination rate (%), G-index value and growth (mm) decreased significantly, suggesting their toxic effect on B. rapa var. turnip. This study further revealed that experiment with seed washing resulted in less toxicity of selected heavy metals on germination and growth of B. rapa var. turnip, as compared to experiment without washing. However, the resulting toxicity order of the selected heavy metals remained the same (Cd > Cr > Pb). Significant decrease has been observed in seed viability and germination potential and finally heavy metals completely ceased further growth and development of plants. The 2, 2-diphenyl-1-picrylhydrazyl (DPPH)-scavenging activity revealed that significantly higher activity was observed in control plants without heavy metals treatment. Furthermore, the Cd-treated plants showed decreased antioxidant activity. Cr and Pb were less toxic as compared to Cd (control > Pb > Cr > Cd). This study revealed that selected heavy metals not only affected plant development but also disturbed plant metabolic pathways.
Probiotics are known as living, nonpathogenic microorganisms that colonize the intestine and provide benefit to the host. The present study aims to measure one important energy metabolism-related enzyme activity in blood of rabbits fed on probiotics of recommended concentration. In addition, it also aims for the evaluation of the expression level of lactate dehydrogenase (LDH) enzyme using reverse transcriptase-polymerase chain reaction (RT-PCR) technique. Two groups of rabbits are used: control group receiving normal standardized diet and the other probiotic-supplemented group receiving the same diet containing probiotic, namely, Mega acidophilus (200 million cfu/kg body weight/day) for 4 weeks. The obtained results revealed that the rabbits supplemented with probiotics showed a significant decrease in the levels of serum total cholesterol (TC), triacylglycerol, high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) when compared with control group. Risk factors detected by measuring TC/HDL-c and LDL-c/HDL-c ratios showed statistically significant decrease in probiotic-supplemented rabbits when compared with control group. In addition, blood glucose and total LDH activity were elevated in probiotic-supplemented rabbits when compared with control group. RT-PCR products of LDH-M gene produced two specific amplicons. One amplicon has the expected size of 243 bp from all samples of rabbits as revealed by GelPro software. The level of LDH-M expression was found to be increased in the probiotic-supplemented group. However, unexpected amplicons are produced at 586 bp in all the samples, which may be a dimeric form of the amplified region. It was concluded that this probiotic blend is beneficiary for the metabolic reactions of lipids in the body. Moreover, LDH expression level can be considered as a biomarker for the effect of probiotic and hence monitoring the metabolic changes as reflected from its administration.
Deltamethrin is globally used in crop protection and control of malaria and other vector-borne diseases. It has a potent insecticidal activity with an appreciable safety margin. However, a number of studies have demonstrated nephrotoxicity of deltamethrin in mammalian and nonmammalian species. Lycopene, a carotenoid occurring naturally in tomatoes, has attracted considerable attention as an antioxidant. This study was focused on investigating the possible protective effect of coadministration of lycopene on deltamethrin toxicity. In this study, male albino rats were divided into four groups of 10 animals each: group I served as control, which received standard diet; group II received oral administration of deltamethrin (1.28 mg/kg per day) for 30 days; group III received both deltamethrin and lycopene (1 mg/kg per day); group IV received lycopene (1 mg/kg per day). After the experiment, the animals were anesthetized and the cytokine, tumor necrosis factor-α (TNF-α), in the serum was measured; the kidney was taken for histological and ultrastructural studies. Deltamethrin significantly increased the TNF-α. The histopathological examination of kidney showed mild necrotic changes. Ultrastructural changes in renal proximal tubules of deltamethrin-treated group included an increased number and irregular shape of mitochondria with sparse fragmented cristae, serious ultrastructural lesions in renal proximal tubular lining cells, vacuolar degeneration in the epithelial cells, increased number of lysosomes and loss of apical microvilli. In addition, focal segmental thickening and the duplication of glomerular basement membrane and podocyte changes were observed. Histopathological and ultrastructural study showed some protective effect of lycopene on kidney tissues.
Aflatoxins (Aspergillus flavus toxins (AFT)) are biologically active secondary metabolites mostly produced by some Aspergillus species that causes hepatotoxicity, teratogenicity, immunotoxicity, and cancers in human. The aim of this study is to determine the level of total AFT in powdered red pepper in the retail markets in 40 district of Istanbul using enzyme-linked immunosorbent assay. Of the 36 unpacked powdered red pepper samples, 32 samples (88%) contained AFT in the range of 0.2–106.4 µg/kg; 16 samples (44.4%) were above the regulatory limit which is at 10 µg/kg for total AFT in Turkey. More precautions on the production, transport, harvest, and storage of red pepper should be taken on hygiene to prevent toxic and carcinogenic effects of AFT.
Skin decontamination is the primary intervention needed in chemical, biological and radiological exposures, involving immediate removal of the contaminant from the skin performed in the most efficient way. The most readily available decontamination system on a practical basis is washing with soap and water or water only. Timely use of flushing with copious amounts of water may physically remove the contaminant. However, this traditional method may not be completely effective, and contaminants left on the skin after traditional washing procedures can have toxic consequences. This article focuses on the principles and practices of skin decontamination.
Phytoremediation is the technology of purging soils and water systems from heavy pollutant metals. Cadmium is one of the heavy elements, which is environmentally important due to its toxicity to humans and animals. Toxicity and accumulation of cadmium in body organs through eating contaminated food has an important role in endangering human’s health. To this end, trees of buttonwood were prepared and irrigated with nutrient solution containing cadmium chloride in 10, 15 and 20 mM for 12 months. Then the root, stem and leaf samples were harvested and the amounts of cadmium element in stem, root and leaf organs together with the growth parameters were measured. This study determined the amount of cadmium accumulated by Platanus occidentalis. Furthermore, the comparison between accumulation and transfer of cadmium in the study showed that absorption of this metal by the root is more than its amount in stem and leaf. The result of this research shows that buttonwood has the potential for cadmium accumulation without any serious damage to its growth. Regarding the extent of contaminated industrial areas, petrochemical industry, power plants and vast contaminated municipal areas, there is a great need for planting fast-growing and tolerant plants like buttonwood.
In this study, the effect of aqueous extract of Crocus sativus L. (saffron) stigma was studied against subacute toxicity of diazinon (DZN) on specific biochemical markers in rats. Vitamin E (200 IU/kg) and the aqueous extract of saffron at doses 50, 100 and 200 mg/kg were injected intraperitoneally three times per week alone or with DZN (20 mg/kg/day, orally) for 4 weeks. Red blood cell (RBC) cholinesterase activity was inhibited by DZN and this effect was not affected by vitamin E or saffron plus DZN. The levels of serum tumor necrosis factor-α (inflammation marker), direct 8-iso-prostaglandin F2α (oxidative stress marker) and soluble protein-100 β (S100β, neuronal damage marker) were increased significantly by DZN. The saffron extract inhibited the effect of DZN on these biomarkers levels. However, vitamin E was able to only reduce 8-iso-prostaglandin F2α and S100β levels. This study showed that the aqueous extract of saffron prevents DZN-induced rise of several specific inflammation, oxidative stress and neuronal damage biomarkers.
Mercury and arsenic pollution has been recognized as a potential environmental and public health problem for over 40 years. The major source of exposure to mercury and arsenic for humans is the ingestion of sea food. Concentrations of mercury and arsenic in the muscle samples of green tiger shrimp (Penaeus semisulcatus) from the Persian Gulf were determined by cold vapor atomic absorption spectrometry. Concentrations of metals in muscle samples were 49–115 µg kg-1 for mercury, 115–131 µg kg-1for arsenic, with means of 82.7 and 251.6 µg kg-1, respectively. Statistical analysis showed no significant difference of mercury and arsenic concentration in shrimp muscles between selected stations (Bushehr, Khuzestan, and Hormozgan provinces). No significant difference was found among heavy metal contents of male and female shrimps. The results of this study indicate that the green tiger shrimp from the Persian Gulf have concentrations well below the maximum permissible levels for mercury (500 µg kg-1) and arsenic (6000 µg kg-1), according to international standards, with no health risk of consumers.
This experiment is designed to investigate the positive effects of commercial nanosilver compound on blood parameters in experimental aflatoxicosis in broiler chickens. For this, 270 one-day-old broiler chickens were randomly divided into six treatment groups with three replicates. The experimental groups were group A: chickens fed with basal diet; group B: chickens fed with 3 ppm productive aflatoxin in basal diet; groups of C, D, E and F received Mycoad (2.5 g/kg diet), Mycoad (2.5 g/kg diet) + productive aflatoxin (3 ppm), Nanocid (2500 ppm), and Nanocid (2500 ppm) + productive aflatoxin (3 ppm) in basal diet, respectively. Results revealed that some of the blood parameters such as mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration lymphocytes, neutrophils, basophils, monocytes, and eosinophils percentage were not affected in this experiment; whereas, hemoglobin percentage and white blood cell (WBC) count in all the groups fed with 3 ppm aflatoxin except nanocid + aflatoxin decreased significantly (p < 0.05). There are no significant differences between the groups that received nanocid + aflatoxin and mycoad + aflatoxin in hemoglobin percentage and WBC count parameters. The red blood cell count and hematocrit in chickens received aflatoxin were significantly lower than other groups (p < 0.05). Therefore, this study suggests that nanocid similar as mycoad can be useful in reducing the adverse effects of aflatoxin on blood parameters in chickens affected with aflatoxicosis.
Bisphenol A (BPA) is a chemical estrogen widely used in the food packaging industry, especially in baby bottles. Its toxicity for the fetus has become a great concern in recent years. In the present study, the effects of BPA on the development of central immune organs in chick embryos were investigated. A total of 30 specific-pathogen-free (SPF) chick embryos were divided into BPA, control, and vehicle group. Chick embryos were exposed to BPA (250 μg per egg), saline (control), or corn oil (vehicle) on embryonic day 9 (ED9) by injection into the allantoic cavity. Thymuses and bursae of Fabricius were collected on ED22. The microscopic examination of tissue structure and ultrastructure was carried out for histopathological changes of thymus and the bursa of Fabricius morphology under light and scanning electron microscopes (SEM). In the BPA group, the weight index of the bursae of Fabricius was significantly reduced (p < 0.01); the number of lymphatic follicles in the bursae of Fabricius was remarkably decreased (p < 0.01); and the thickness of the thymus cortex and medulla was reduced (p < 0.01). Light microscope and SEM examinations further showed that the lymphatic follicles and epithelial cells of the bursa of Fabricius and thymus were damaged by BPA. Our study confirms a direct toxicity of BPA at a very low-dose level on the development of the central immune organs of SPF chick embryos. However, more studies are necessary to elucidate the underlying mechanisms.
Evidence indicates that optimal nutrition plays a role in bone formation and maintenance. Besides major components of mineralization such as calcium, phosphorus, and vitamin D, other nutrients like boron and fluoride have beneficial role, too. In this study, 34 male Wistar rats were divided into five groups: control diet, fluoride, fluoride + boron, fluoride + calcium + vitamin D, and flouride + boron + calcium + vitamin D. Boron equal to 1.23 mg, calcium and vitamin D equal to 210 mg + 55 IU and fluoride equal to 0.7 mg/rat/day was added to their drinking water for 8 weeks. Plasma blood samples and bones were collected. Findings are evidence that fluoride + boron intake revealed significant positive effects on bone mechanical properties and bone metabolic hormones. These findings suggest that combined intake of these two elements has beneficial effects on bone stiffness and breaking strength comparing to even calcium + vitamin D supplementation. This evidence dealing with health problems related to bone and skeletal system in humans should justify further investigation of the role of boron and fluoride with other elements in relation to bone.
Cigarette smoking is the major risk factor for smoking-related interstitial fibrosis (SRIF). Despite recent advances, the molecular mechanisms involved in the initiation and progression of this disease remain elusive. We found 6 months of chronic mainstream smoking exposure induced SRIF in C57 mice, which was associated with pronounced enhanced oxidative stress, bronchoalveolar inflammation and fibrosis but not apoptosis of alveolar septal cell. We used Affymetrix microRNA (miRNA) arrays to determine the temporal alteration in global gene expression of peripheral blood during the progression of diffuse pulmonary interstitial fibrosis in C57 mice. Microarray analysis revealed the upregulation of 3 miRNAs (miR-92b, miR-700 and miR-668) and the downregulation of 5 miRNAs (let-7e, miR-142-5p, miR-350, miR-19a and miR191*) in the peripheral blood of mice exposed to mainstream smoking for 1, 2, 3 and 6 months. We proposed that circulating miRNAs might be promising biomarkers to reflect the dynamic pathological changes of SRIF related interstitial fibrosis.
The purpose of this study was to evaluate the effect of carotenoid astaxanthin (ASTA) on cultured primary rat hepatocytes treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the cell viability (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, MTT), lactate dehydrogenase (LDH) activity, 8-oxo-2-deoxyguanosine (8-OH-dG), total antioxidant capacity (TAC), and total oxidative stress (TOS) levels, and liver micronucleus rates. ASTA (2.5, 5, and 10 µM) was added to cultures alone or simultaneously with TCDD (5 and 10 µM) for 48 h. The results of MTT and LDH assays showed that both doses of TCDD caused significant decrease in cell viability. Also, TCDD significantly increased TOS and decreased TAC level in rat hepatocytes. On the basis of increasing doses, the dioxin caused significant increase in micronucleated hepatocytes) and 8-OH-dG level as compared to control culture. The presence of ASTA with TCDD minimized its effects on primary hepatocytes cultures and DNA damages.
The effect of long-term exposure of goldfish to dietary genistein and diadzein on the concentrations of plasma sex steroids (testosterone (T), 17β-estradiol (E2)) and the gonadosomatic index (GSI) was assessed. The study was conducted on four groups for a period of 2 years, from the age of 20 weeks to first spawning. Four doses of genistein and diadzein were applied in the feed: genistein: 0 µg/g, diadzein: 0 µg/g (control group); genistein: 24.26 µg/g, diadzein: 21.7µg/g (diet 1); genistein: 51.55 µg/g, diadzein: 46.13 µg/g (diet 2); and genistein: 75.83 µg/g, diadzein: 67.82µg/g (diet 3). Throughout the experiment, there were no significant dose- or time-related effects of genistein and diadzein contents on the T level in both sexes. Furthermore, at the highest genistein and diadzein contents, there was an elevating plasma concentration of E2 at all sampling points (p < 0.05) and a time-related effect occurred (p < 0.05). Although the E2 concentrations in the plasma of female, throughout the experiment, were higher than in males, at the last sampling, the plasma concentrations of E2 reduced among females and became lower than that in males. The effects of isoflavone content were found on GSI of females at the fourth and fifth sampling among the treatments. Isoflavone contents also affect GSI of males at the second, fourth and the last sampling. Our findings suggest that overall genistein and diadzein exposure in early life stages can cause alterations in the reproductive organs and influence sex steroidogenesis.
Formaldehyde (FA) is widely used in industrial and medical settings. It has long been suspected of causing adverse reproductive and developmental effects. However, the effects of exposure to FA on the reproduction are still a matter of scientific controversy. In this study, we evaluate the hypothesis that adverse developmental outcomes of the exposure to FA might be due to its effects on the placental structure. So, histological changes of the placenta in the mice exposed to FA gas were assessed at light and electron microscopy levels. A total of 40 pregnant Balb/C mice were randomly allotted to four groups in which the animals were exposed to FA at the doses of 0 (control), 7, 14 and 28 ppm, respectively, by inhalation, consecutively, for 8 h/d during the organogenesis period. On day 17 of gestation, the animals were killed and the histological specimens of the placentas were taken for light and electron microscopy studies. Also, morphological parameters of the placentas were measured manually. The results showed that the effects of FA on the placenta are not dose dependent. In the FA-exposed mice, an increase in the number and size of trophoblastic giant cells and an enlargement of spongiotrophoblastic cells in the basal zone of placenta were seen. Also, a significant increase in placental weight as well as the ratio of placental to fetal weight but a decrease in the fetal weight were found in the treated groups when compared with those in the control mice (p < 0.05). Moreover, ultrastructural results demonstrated that the diameter of labyrinth interhemal membrane as well as the thickness of trophoblastic basement membranes were significantly increased in the FA-exposed mice. In addition, in the FA-treated animals, a severe accumulation of cytoplasmic droplets in the II and III trophoblastic layers of the placenta were seen. In conclusion, this study may suggest that the exposure to FA during the organogenesis period at doses of 7–28 ppm induces toxic changes in the placental structure. These changes disrupt placental functions and leads to a decrease in the fetal weight.
Aqueous extract (AE) of Hammada scoparia leaves was chemically characterized and its hepatoprotective activities were investigated in vivo in rat model. Wistar rats were treated daily with 35% ethanol solution (3 g/kg/day) during 4 weeks and fed with basal diet or basal diet containing AE (200 mg/kg/day). Control rats were treated with saline solution and fed with basal diet. The bioactivity of AE against ethanol-induced oxidative stress in rat liver was studied in order to explore its hepatoprotective effects. H. scoparia extract used at 200 mg/kg body weight significantly prevented the effects of ethanol, which induced a hepatic pathological damage and increased the levels of the serum markers of the enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). Concomitantly, with these changes, this extract also prevented ethanol-induced oxidative stress in the rat liver as evidenced by the decreased lipid peroxidation level, a considerable decrease in the activities of AST, ALT and ALP and restoring the activities of antioxidant enzymes: superoxide dismutase, catalase and glutathione peroxidase. These biochemical changes were consistent with histopathological observations suggesting marked hepatoprotective effect of the AE of H. scoparia.
Nuclear medicine has been using radiopharmaceuticals for the diagnostic and therapeutic purposes of many diseases. Technetium-99m methoxyisobutylisonitrile (99mTc sestamibi) is a lypophilic complex that has a positive-loaded isonitril group. Aim of the study is to investigate whether 99mTc sestamibi, which is one of the mostly used radiopharmaceuticals in nuclear medicine field, causes oxidative damage or not in rats’ heart after an injection. A total of 16 male Sprague Dawley rats were randomly divided into two groups: group I: 99mTc sestamibi group, 99mTc sestamibi administered intravenously with the dose of 25MBq; group II: control group, one dose of isotonic sodium chloride was administered intravenous with the same volume as 99mTc sestamibi group. Malondialdehyde (MDA) and total oxidant status (TOS) were used as markers of oxidative stress-induced heart impairment. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and total antioxidant status (TAS) activities were studied to evaluate the changes in the antioxidant status. In the 99mTc sestamibi group (group I), animals treated with 99mTc sestamibi produced a significant decrease in the activities of antioxidant enzymes (SOD and CAT), while MDA level increased when compared with control group (group II) in myocardial tissue (p < 0.05). On the other hand, the GSH-Px activities were significantly increased in the 99mTc sestamibi-treated rats compared with the untreated rats (p < 0.05). There was no significant difference in the TAS and TOS levels of plasma.
Ochratoxin A (OTA) and citrinin (CIT) are nephrotoxic mycotoxins produced mainly by fungal species Aspergillus ochraceus and Penicillium citrinum, respectively, which have been found to occur together in various food and feed commodities. In the present study, both OTA and CIT were evaluated for their potential to induce oxidative damage by determining lipid peroxidation (LPO) through malondialdehyde (MDA) assay and apoptosis by flow cytometry, gel electrophoresis and renal ultrastructural morphology in rabbits fed with diets containing OTA (0.75 mg/kg feed), CIT (15 mg/kg feed) and OTA + CIT (0.75 and 15 mg/kg feed, respectively) up to 60 days. The concentration of MDA was found significantly higher in OTA and combination-treated groups. OTA and combination-treated groups revealed more apoptotic cells in flow cytometry when compared with the CIT-treated group. Characteristic DNA fragmentation, as evidenced by ladder pattern in electrophoresis appeared in the toxin-treated groups. Ultrastructurally, interstitial cells showed nuclear fragmentation and cytoplasmic blebbing in OTA- and CIT-treated groups; whereas, proximal convoluted tubular epithelial cells, besides interstitial cells, showed nuclear fragmentation in the combined treatment group. The results suggested that low concentrations of OTA and CIT either alone or in combination induced apoptosis in a time-dependent manner and LPO in the rabbit kidney, which appeared to play a major role in the pathogenesis of nephrotoxicity. Furthermore, the interaction of these two nephrotoxic mycotoxins was found to be additive.
The aqueous and methanolic extracts of Calligonum comosum were investigated for their antioxidant and dopaminergic effects on haloperidol (HL)-induced neuro- and hepatotoxicities in male albino rat model. The total phenolics, flavonoid content and free radical-scavenging activity of the extracts were determined. The results showed that the antioxidant activity of the methanolic extract was higher than the aqueous one. HL significantly reduced GSH and increased MDA in brain and liver tissues. These values were nearly normalized, in the examined tissues, on concomitant administration of C. comosum methanolic extract with HL. Superoxide dismutase activity in the examined tissues was significantly decreased by HL administration that was normalized by the coadministration of the methanolic extract and, to a less extent, the water extract. Determination of the brain neurotransmitter contents revealed a marked decrease in norepinephrine, dopamine and serotonin, which were restored to near control values by concomitant administration of both C. comosum extracts with HL. The results of this study showed that C. comosum methanolic and aqueous extracts ameliorated HL-induced neuro- and hepatotoxicities in rats.
The planarians (Dugesia japonica) are distributed widely in China, Japan, Korea, and southern Siberia. In this study, the acute toxicity of copper on D. japonica was evaluated using mortality and the activity of the enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), and reactive oxygen species (ROS) as endpoints. Acute toxicity tests were conducted according to the American Society for Testing and Materials guidelines. The 24-, 48-, 72-, and 96-h median lethal concentration that killed 50% of individuals (LC50) were calculated as 8.70, 6.31, 4.48, and 4.23 mg Cu2+/L, respectively, based on measured copper concentrations. When compared with different phyla or classes of freshwater animals, the rank of D. japonica in species sensitivity was in the range of 25–26 for 96-h LC50. The antioxidant enzymes SOD and CAT were determined in D. japonica exposed to two copper concentrations (50 and 100 μg Cu2+/L) with a short-term exposure (15 days). They all attained peak value and then reduced during the experimental period. The GPx activities were activated only for 100 μg/L treatments at days 3 and 6 and then renewed to the original level. Meanwhile, copper significantly increased the levels of ROS in D. japonica. Our study suggests that the adult D. japonica was less sensitive to copper than most other aquatic species. Copper may induce oxidative stress and interfere with the antioxidant defense system of the D. japonica, including SOD and CAT. GPx might be an insusceptible antioxidant enzyme in the metabolic detoxification processes in adult D. japonica.
Phenolic compounds are common water pollutants and include a wide variety of organic chemicals. The effects of three sublethal concentrations of phenol on liver histology and some biochemical parameters of Oncorhynchus mykiss after 8 weeks exposure were investigated in this study. A total of 80 rainbow trout (O. mykiss) were randomly divided into four groups (n = 20). Control group was kept in water without any add-on material, while experimental groups were exposed to the concentration of 0.6, 1.2 and 2.4 mg/L of phenol solution. At the end of the study period, the weight of liver, condition factor (CF) and hepatosomatic index (HSI) were measured. Tissue and blood samples were taken separately for histologic evaluation and serum biochemical parameters assay, respectively. In fish treated with phenol, significant reduction in liver weight, CF, HSI ratio, diameter of hepatocytes and hepatocytes nuclear diameter (p < 0.05) was recorded. Total protein and albumin decreased significantly in treated fish in comparison with control (p < 0.05), but levels of cholesterol, glucose, alkaline phosphatase, lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase in fish exposed to different concentrations of phenol showed a significant increase (p < 0.05). These findings showed that phenol could cause its harmful impacts even in very low concentrations.
Many episodes of low back pain are disabling, thus making it one of the costly occupational health problem. The proper alignment and lifting operations during drilling process frequently exposed the oil-drilling workers to unusual strain on the spine and thus make them susceptible for developing low back pain. The present cross-sectional study was carried out in 71 oil-drilling workers. The prevalence of self-reported low back pain was found to be 29.6%. Higher prevalence was found in those working in awkward working posture (c2 = 6.41; df = 1; p < 0.01). No other factors, namely, age, obesity, duration of exposure, smoking habit, family history of musculoskeletal disorders, exposure to vibration, lifting of weights and past history of injury was found to be statistically significant. Furthermore, using univariate and multivariate analysis, none of the factor was found to have excess risk of occurrence of low back pain, which can partly be attributed to small sample size.
This study determined the concentration of heavy metals (Al, Cr, Cu, and Zn) in water and sediments at nine sites in the Hara biosphere reserve of southern Iran during the summer and winter 2010. Determination of Al, Cr, Cu, and Zn in water was carried out by graphite furnace atomic absorption spectrometer (Shimadzu, AA 610s) and in sediment by flame atomic absorption spectrometer (Perkin Elmer, AA3030). Results showed that the heavy metal concentrations in the water samples decreased in the sequence of Zn > Al > Cu > Cr, while in sediment samples were Cr > Zn > Cu > Al. Data analysis indicated that with the exception of Al, there was a Pearson’s correlation coefficient between pH and Cu, Zn, and Cr at α = 0.01, 0.05, and 0.001 in sediment (in winter), respectively. There were also significant differences between heavy metals of Cr, Cu, and Zn during the two seasons (p < 0.001) in the water and sediment.
Naphthalene, a bicyclic aromatic hydrocarbon, has toxic effects on animals and humans. Although recent studies stressed on the genotoxic and cytotoxic effects of naphthalene and its metabolites on eukaryotic cells, there is a big controversy among the results of these studies. The aim of this study is to investigate the effects of naphthalene and its metabolites on the cytotoxicity and genotoxicity in the human lymphocytes in the culture. The genotoxic and cytotoxic effects of naphthalene and its metabolites, 1-naphthol and 2-naphthol, were studied using cytotoxicity test (lactate dehydrogenase and cell proliferation (WST-1) assays) and DNA fragmentation assay (terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay). Naphthalene and its metabolites had no significant cytotoxic effect on treated samples when compared with untreated ones. This result was also confirmed by WST-1 assay. In the TUNEL assay, DNA fragmentation was induced significantly by all concentrations of naphthalene and 2-naphthol and 50 and 100 µM concentrations of 1-naphthol (p < 0.05 or 0.001). In the DNA fragmentation, the most effective dose of 2-naphthol (63%) was 100 µM, when compared with negative control group (13%). These results suggest that naphthalene and its metabolites, 1-naphthol and 2-naphthol, may cause DNA damage on human lymphocytes.
We report seven cases of acute myeloid leukemia (AML) with occupational exposure to a toluene-based hydrocarbon solvent. The cases were employed at a facility, which manufactured rubber belts and hoses, between 1950 and 2005 for periods ranging from 21 to 37 total years. Detailed histories were obtained for three workers who were diagnosed with AML within a 3-year period (2003–2005). Death certificates, medical records, and accounts by workers were reviewed. Benzene, a known cause of AML, is typically a contaminant of toluene. Benzene contamination in toluene and other widely used solvents and the potential for concurrent benzene exposure during usage of these solvents in occupational settings are discussed.
Epirubicin (EPI) is one of the anthracycline antibiotics, which is used in cancer chemotherapy. It inhibits DNA and RNA synthesis and causes cell death by DNA cleavage and production of free radicals. In this study, phytotoxicity of EPI was investigated on root and shoot growth, antioxidant enzymes and retrotransposons’ movements in 10- and 20-day-old barley seedlings. Mature embryos of barley were germinated on Murashige and Skoog medium supplemented with 250 and 500 μg/ml EPI. Our results showed that EPI treatment significantly inhibited shoot and root growth when compared with control group. Treatment with 250 and 500 μg/ml of EPI reduced shoot length in the 10-day-old plants by approximately 1.5- and 2-fold, respectively; the same treatments reduced total root length by 2- and 4-folds, respectively. However, the shoot and root lengths of 20-day-old plants were observed to be more affected by EPI-treatment. A 500-μg/ml concentration decreased total protein levels and peroxidase (EC 1.11.1.11) activity and increased superoxide dismutase (EC 1.15.1.1) and catalase (EC 1.11.1.6) activities. To investigate the effect of EPI on the movements of BARE-1, SUKKULA and BAGY2 retrotransposons, inter-retrotransposon amplified polymorphism technique was performed. While some polymorphic polymerase chain reaction bands were observed for BARE-1, no polymorphism was identified in SUKKULA and BAGY2 movements. To our knowledge, this is the first report showing phytotoxic effects of EPI on plant germination and retrotransposons’ movements.
The aim of this study is to evaluate the influences of short-term treatment with levosimendan (chemical formula: C14H12N6O) on oxidative stress and some trace element levels in renal tissues of healthy rats. A total of 20 male Wistar-albino rats were randomly divided into two groups, each consisting of 10 rats. Animals in the first group were not treated with levosimendan and served as control. Animals in the second group were injected intraperitoneally with 12 µg/kg levosimendan and served as levosimendan group. Animals in both the groups were killed 3 days after the treatment, and their kidneys were harvested for the determination of tissue oxidant/antioxidant statues and trace element levels in renal tissues. The tissue malondialdehyde level was significantly (p < 0.001) lower in levosimendan group than in controls. The protective enzyme activities such as superoxide dismutase, catalase, and glutathione peroxidase and antioxidant glutathione level were significantly (p < 0.001) higher in levosimendan group than in controls. It was concluded that levosimendan reduced oxidative stress by avoiding lipid peroxidation and production of reactive oxygen species, and overactivating and/or increasing the protective antioxidant enzyme levels in renal tissues of rats. It is supposed that this experimental study provides beneficial data for clinicians in the management of renal tissue damage related to obstruction and/or ischemia.
Microbiological studies were carried out on microbial contamination and antimicrobial activity of sea cucumber Holothuria polii collected from Mediterranean Sea at Abu-kir shore of Alexandria, Egypt. The obtained results revealed the presence of isolates of five human Gram-negative pathogenic bacteria, representing five genera were identified to species level, including, Esherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella sp. and Shigella sp. In addition, an yeast Candida albicans was isolated. The pathogenic bacteria were identified using API 20E strip system (BioMereux). All collected H. polii specimens were healthy with no external signs of infection. Histopathological study of the tegument, intestine and gonads showed no abnormal changes. The antimicrobial activity of two tegumental ethanol extracts (A and B, differ in the method of dehydration) were tested against wide range of pathogenic bacteria and fungi, including intestinal, skin and nosocomial pathogens and one plant fungal pathogen. The results revealed a remarkable antifungal activity of the extract B at 2.5 mg/ml MIC90, especially on Aspergillus niger, Scloretium sp, C. albicans, Aspergillus flavus and Malassezia furfur, and limited antibacterial activity against Gram-negative bacteria (Salmonella choleraesuis ATCC 14028 and Aeromonas hydrophila). The domain of bacterial and limited fungal contamination confirms the results that showed strong antifungal activity of investigated extract.
Deltamethrin (DEL) and thiacloprid (THIA) are the two commonly used synthetic insecticides applied either separately or as a mixture. The aim of this study was to assess thyroid stimulating hormone (TSH) and the serum levels of thyroid hormones exposure to these compounds in rats. The animals were orally gavaged with a single dose of DEL (15 mg/kg), THIA (112.5 mg/kg) or DEL + THIA (15 + 112.5 mg/kg) for 24 h (acute treatments) or DEL (3 mg/kg per day), THIA (22.5 mg/kg per day) or DEL + THIA (3 + 22.5 mg/kg per day) for 30 days (subacute treatments). Although all independent and combined treatments with DEL and THIA changed the levels of TSH, these alterations were not significant. Statistically significant increases in free triiodothyronine (FT3) and free thyroxine (FT4) serum hormone levels were observed in the independent treatment with THIA and the combined treatment with DEL and THIA for 30 days. The results of this study suggest that in vivo exposure to subacute treatments of commercial formulations of THI and mixture of DEL + THIA increased serum FT3 and FT4 levels in rats. Further studies are required to determine the effects of endocrine disruptors and potential health risks of these insecticides in human, especially in children because of the importance of these hormones during growth and development.
In this present study, antioxidant status was evaluated in rat serum following exposure to magnesium oxide (MgO) nanoparticles. The lungs of rats were intratracheally instilled with (single dose) phosphate-buffered saline (PBS) + 1% of Tween 80 (solvent control) or MgO or carbonyl iron (negative control) or quartz particles (positive control) at a dose of 1 and 5 mg/kg of body weight. The blood samples were collected at 1, 7, and 30 days of postinstillation of nanoparticles after their exposure, and different parameters were estimated to assess the oxidative stress induced by the instillation of MgO. Exposure of rats to MgO produced a significant (p < 0.05) dose-dependent reduction in blood total antioxidant capacity, superoxide dismutase, and catalase activity levels than PBS + 1% Tween 80 control group. This reduction in the antioxidant capacity in MgO nanoparticle-exposed rats indicates the reduction in antioxidant defense mechanisms due to the instillation of MgO. These results indicate that exposure to MgO nanoparticles induces oxidative stress by reducing the total antioxidant capacity in rats. The findings suggest possible occupational health hazard in chronic exposures.
In recent years, a number of studies have suggested that lichens might be the easily accessible sources of natural drugs that could be used as a possible food supplement. Extensive research is being carried out to explore the importance of lichen species, which are known to contain a variety of pharmacological active compounds. On the other hand, imazalil (IMA), a commonly used fungicide in both agricultural and clinical domains, is suspected to produce very serious toxic effects in vertebrates. In this context, the antigenotoxic effect of aqueous Bryoria capillaris (Ach.) extract (BCE) was studied against the genotoxic damage induced by IMA on cultured human lymphocytes using chromosomal aberrations (CA) and micronucleus (MN) as cytogenetic parameters. Human peripheral lymphocytes were treated in vitro with varying concentrations of BCE (5, 10, 25, 50 and 100 µg/mL), tested in combination with IMA (336 µg/mL). BCE alone was not genotoxic, and when combined with IMA treatment, it reduced the frequency of CAs and the rates of MN. A clear dose-dependent decrease in the genotoxic damage of IMA was observed, suggesting a genoprotective role of BCE. The results of the present study suggest that this plant extract per se do not have genotoxic potential, but can modulate the genotoxicity of IMA on peripheral human lymphocytes in vitro. In conclusion, our findings may have an important application in the protection of cultured human lymphocyte from the genetic damage and side effects induced by agricultural and medical chemicals that are hazardous to people.
Ammonia is a widely used industrial chemical that is recognized as a potent neurotoxin and environmental pollutant. The present study addresses the oxidative stress and tissue pathology caused by 4 weeks of exposure to ammonium acetate (AMA; 100 mg/kg daily; orally) in rats, and their response to oral treatments with alpha-ketoglutarate (A-KG; 1.0 g/kg), a potential cyanide antidote, and/or N-acetyl cysteine (NAC; 10 mg/kg), an antioxidant. The organ–body weight index of brain and liver was significantly increased by AMA but kidney was unaffected. Also, plasma ammonia levels were significantly elevated without any concomitant change in blood gas status and hematology but levels of catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and reduced glutathione (GSH) in the brain and liver were diminished, accompanied by elevated levels of malondialdehyde. Levels of glutathione disulfide (GSSG) were unaffected, but the ratio of GSH:GSSG was reduced. Plasma alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase and total bilirubin were raised but urea, uric acid and creatinine levels were not altered. AMA also caused temporal, hepatic and renal pathology. However, the renal pathology was not supported by any biochemical alterations. A-KG or NAC alone afforded less protection against AMA as compared to both given together. The protective efficacy of A-KG can be ascribed to its ability to detoxify ammonia and additionally both A-KG and NAC have antioxidant properties as well. The study suggests a new therapeutic regimen for ammonia poisoning.
Consumption of alcohol leads to oxidative stress in liver by inducing lipid peroxidation. The aim of this study was to investigate the effects of carnosine (CAR) in alcohol-induced liver injury by biochemical and histomorphological evaluations. The rats were divided into four groups, namely, control group, alcohol (AL) group, CAR group and AL + CAR group. Three doses of ethanol (5 g/kg, 25% (v/v) in distilled water) were given by nasogastric catheter for twice-a-day. CAR (100 mg/kg) was given 1 h before the administration of ethanol using the same method. Levels of alanine aminotransferase, aspartate aminotransferase, myeloperoxidase and malondialdehyde were significantly increased in the AL group compared with control, CAR and AL + CAR groups. Glutathione level was significantly decreased in the AL group, while it was increased in the AL + CAR group. Immunoreactivity of caspase-3 and bax increased in the hepatocytes of AL group when compared with control and AL + CAR groups. Expression of bcl-2 was decreased in AL group than AL + CAR group. Under electron microscopy, dense mitochondria, accumulation of lipid, sinusoidal dilatation, vacuolization and decrease in the number of microvilli were observed in AL group, while these findings were markedly less in the AL + CAR group. In conclusion, pretreatment of CAR is effective for recovering biochemical alterations and morphologic damage in the liver of rats treated with ethanol.
Molecular mechanisms in the pathogenesis of silicosis are not fully understood. Exposure to crystalline silica leads to the activation of signaling pathways controlling the production and secretion of inflammatory mediators. Inflammatory cytokines are noted as important candidate genes for fibrotic lung diseases. Cytokines, chemokines, and variations of their genes have been associated with upregulation or downregulation of chronic inflammatory mediators. Variations in the interleukin (IL)-18, IL-8 and chemokine receptor CXCR2 genes are believed to influence the risk of silicosis in stone-grinding factory workers in Iran. Allele-specific oligonucleotide polymerase chain reaction (PCR) procedure was carried out for IL-18 -137 and IL-18 -607, meanwhile touchdown PCR was performed for IL-8 -251 and CXCR2 +1208 genotyping. Variation in genotypic and allelic frequencies was not statistically different among cases versus controls (p > 0.05). These findings indicated for the first time that IL-18 -137, IL-18 -607, IL-8 -251, and CXCR2 +1208 are suggested not to influence the risk of silicosis in tested occupational group.
Smoking is still a major public health problem in Turkey. It was aimed to investigate smoking prevalence and habits among Turkish family physicians. Cross-sectional study among physicians working in primary care settings was established. A self-administered study survey was applied. The surveys of 1233 family physicians were analyzed. The study included 704 (57.1%) male and 529 (42.9%) female physicians. Mean age (SD) was 38.94 (7.01) years. The proportions of the current, the former and never smokers among family physicians were 34.1%, 14.7% and 51.3%, respectively. Mean age (SD) of smoking initiation was 21.73 (5.04) years. Mean duration (SD) of smoking use was 14.61 (7.29) years. Proportion of current smoker in male physicians was quite higher than in female counterparts (36.9% vs. 30.4%; p < 0.001). Mean age (SD) of smoking initiation in female was 21.42 (4.59) years, but in male was 22.33 (4.98) years (p = 0.36). In female physicians, mean age (SD) for quitting cigarette smoking was found higher than in male (35.85 (6.35) years vs. 33.09 (6.45) years; p = 0.004). No significant difference between nicotine dependence (mean score (SD) of 3.76 (2.48) vs. 3.65 (2.82); p > 0.05) and mean (SD) unit of cigarette a day (18.34(6.03) vs. 17.17 ± 6.79; p > 0.05) between genders was observed. The number of male physicians who started smoking before faculty was higher than female counterparts (15.5% vs. 8.6%; p = 0.023). In conclusion, the smoking prevalence among Turkish family physicians is considerably high.
Bisphenol A (BPA) is one of the highest volume chemicals produced worldwide. BPA is used in the production of polycarbonate plastics and epoxy resins used in manufacturing plastic baby bottles and lining of food cans. In this study, we investigated the BPA-induced testicular oxidative stress and perturbation of mitochondrial marker enzymes in male albino rats and its amelioration by α-lipoic acid (LA). Rats were administered a dose of BPA (10 mg/kg body weight) orally for 14 days. This resulted in decreased testes weight, total testicular protein content, testicular enzymes such as acid phosphatase, alkaline phosphatase and lactate dehydrogenase and decline in activities of marker mitochondrial enzymes such as succinate dehydrogenase, malate dehydrogenase, isocitrate dehydrogenase, monoamine oxidase and NADH dehydrogenase. The serum testosterone and total antioxidant status were reduced. Besides, it also affected the activities of testicular antioxidant enzymes such as glutathione reductase, glutathione peroxidase, superoxide dismutase and catalase. BPA also caused lipid peroxidation and decrease in reduced glutathione content of mitochondria. The co-administration of LA (20 mg/kg body weight; orally for 14 days) together with BPA resulted in restoration of the mitochondrial marker enzyme activities and increasing enzymatic and non-enzymatic antioxidants of mitochondria. The obtained results demonstrated that LA has a potential role in mitigating BPA-induced mitochondrial toxicity through antioxidant mechanism or by direct free radical scavenging activity.
The aim of this study was to clarify the effects of dietary supplementation with Yucca schidigera (Ys) on lipid peroxidation (LPO), antioxidant activity, some biochemical parameters and histopathological changes in arsenic-exposed mice. Forty Swiss albino male mice were divided into five equal groups. Group I (control group) was given normal diet and tap water for 28 days. Group II (arsenic group) was given normal diet and 100 mg/L arsenic along with drinking water for 28 days. Groups III–V were given three different doses of Ys (50, 100 and 200 mg/kg) in supplemented diet and arsenic (100 mg/L) along with drinking water throughout the entire period of 28 days. The arsenic significantly increased serum biochemical parameters and malondialdehyde levels in blood and tissue. However, arsenic significantly decreased tissue glutathione concentration, erythrocyte superoxide dismutase and catalase activities. In contrast, dietary supplementation of Ys, in a dose-dependent manner, resulted in reversal of arsenic-induced oxidative stress, LPO and activities of antioxidant enzymes. Moreover, Ys also exhibited protective action against the arsenic-induced focal gliosis and hyperemi in brain, necrosis and degeneration in liver, degeneration and dilatation in Bowman’s capsule of kidney and hyaline degeneration in heart tissue of mice. Consequently, our results demonstrate that Ys especially high-dose supplementation in diet decreases arsenic-induced oxidative stress and enhances the antioxidant defence mechanism and regenerate of tissues in Swiss albino mice.
Styrene is a basic building block for manufacturing thousands of products throughout the world.
The present study aimed to (1) detect the presence of styrene and/or its metabolites in the workers in one of the Egyptian plastic factories; (2) demonstrate some common health effects of styrene exposure among the same group by some laboratory investigations and compare them with the unexposed healthy individuals; and (3) correlate the duration of styrene exposure and its level in the blood with the severity of the demonstrated health effects.
This study was conducted in one of Egyptian plastic factories. The exposed group was 40 male workers, ranging in age from 18 to 33 years (23.20 ± 4.09), working 12 h/day with 1 day off, and working without any protective equipment. A control group of 50 unexposed healthy males matched with the exposed group for age (21–35 yrs (23.40 ± 4.05)), sex, socioeconomic status, and smoking habit is selected. Written individual consent is obtained from all participants followed by (a) a full medical and occupational history and full clinical examination; (b) ventilatory function tests: forced vital capacity (FVC), slow vital capacity, forced expiratory volume in the 1st second (FEV1)%, FEV1/FVC%, peak expiratory flow, and mid-expiratory flow 25–75%; (c) analyses of β2 microglobulin; blood styrene level; and urinary mandelic acid; and (d) cytogenetic study.
The study results showed a statistically significant difference between the exposed and the control groups as regard the blood styrene level, urinary mandelic acid level, β2 microgloblin in urine, and chromosomal study. The study also showed a statistically significant correlation between the duration of styrene exposure and ventilatory function parameters, also between the duration of styrene exposure and some detectable chromosomal aberrations.
Our study recommends the implementation of preemployment and periodic medical examinations and health education programs using personal protective equipments and following the recommended allowable concentrations of styrene exposure.
The present study was carried out to determine histopathological effects of nicotine, one of the most significant components of tobacco, on mouse liver and ameliorative effect of melatonin on liver damage. A total of 140 mature Swiss Albino mice (Mus musculus) were divided into four experimental groups: control group, nicotine group, melatonin group and nicotine + melatonin group. Each group was further subdivided into seven groups (five mice each) according to the time of killing (12 h and days 1, 3, 5, 7, 14 and 21 after drug administration). In nicotine and nicotine + melatonin groups, 3 mg/kg of nicotine was injected intraperitoneally every day until killing. The nicotine + melatonin group was additionally injected with 10 mg/kg of melatonin after 30 min of nicotine injection. The melatonin group was injected only with 10 mg/kg of melatonin every day until killing. All the treatments were given 2 h before sunset, when melatonin receptors were active. After the last injection, five mice from each group were killed at 12th hour and on days 1, 3, 5, 7, 14 and 21; the livers were removed for histopathological processing by light microscopy. The histopathological results revealed time-dependent degeneration in the livers of mice in nicotine group. Regenerative changes in the nicotine and melatonin groups were observed when compared with nicotine groups.
Most previous studies focused on a small number of heat shock proteins (Hsps) and their relationships with embryogenesis, and the actual roles of these Hsps in normal and abnormal embryonic development remain unclear. It was found in the present systemic study that except for Grp170, whose expression was not detectable at GD18, all 19 Hsps of Hsp70, Hsp90 and Hsp110 families were expressed in the normal development of embryonic palate tissue in mice, but their expression patterns varied with different Hsps, presenting as a correlation with the developmental phases. In the treatment group by all-trans retinoic acid (atRA), the messenger RNA (mRNA) abundance of HspA1A, HspA1L, HspA8, HspA9, HspA12A, HspA12B, HspA13, HspA14, Hsp90AA1, Hsp90AB1, Grp94, Trap1, Hsp105, Hsp110 and Grp170 was higher in the palates at GD11 (the beginning of palate development), the mRNA abundance of HspA1A, HspA12A and HspA12B was higher at GD18 (before birth) and an mRNA expression peak of HspA1L, HspA8, HspA9, Hsp90AA1, Grp94, Hsp110 and Grp170 was observed at GD17. The mRNA abundance of most genes in atRA-induced cleft palates of the treatment group was different from that of the control group. Grp78, HspA14 and Hsp105 were closely associated with the normal palate development and cleft palate in mouse embryo, possibly as palate development-related genes. Except Grp170, the other genes may be closely associated with the development of mouse palates through participating in the stress response process and/or the antiapoptosis process.
In the present study, the genotoxic and cytotoxic effects of the low-caloric artificial sweetener maltitol, which is a sugar alcohol (polyol), were investigated in the bone marrow cells of rats using the chromosome aberration (CA) test. In addition, the teratogenicity and embryotoxicity of maltitol was also investigated in rats. To reveal the genotoxicity and cytotoxicity of maltitol, rats were intraperitoneally administered 2.5, 5 and 10 g/kg body weight (bw) concentrations of maltitol for 6, 12 and 24 h treatment period. The pregnant females were intraperitoneally treated with 1, 2 and 4 g/kg bw/day concentrations of maltitol during the first 7 days of gestation (first trimester) to investigate the teratogenicity of maltitol. The embryos were collected after killing the dams by cervical dislocation under ether anaesthesia on gestation day 19. Maltitol did not induce the CA and did not decrease the mitotic index in bone marrow cells of rats at all concentrations and treatment periods. In addition, maltitol was not teratogenic; however, it decreased the foetuses weight and at the highest dose (4 g/kg bw) caused growth retardation.
The aim of the present study is to investigate whether or not pulsed electric field (PEF) affects some hematological parameters in rats. Sixteen healthy male Wistar rats weighting 150–200 g were used and were randomly divided into two groups. Exposure group (n = 8) was exposed to a PEF (10 kV m-1 for 1 h d-1) for 10 consecutive days. The control group rats (n = 8) were not exposed to PEF. The following hematological parameters were measured in both the groups: white blood cells (WBCs), red blood cells (RBCs), hemoglobin (Hb), hematocrit (Ht) and platelets (PLTs). Some of the hematological parameters under investigation were similar in both the groups. Exposure group, exposed for 1 h d-1 during 10 consecutive days, induced a significant increase in the rates of WBC (p < 0.05), RBC (p < 0.05), Hb (p < 0.05), Ht (p < 0.05) and PLTs (p < 0.05) in blood when compared with control. These results suggest that PEFs affect the hematological parameters in rat. Results of the parameters are statistically significant.
The aim of this study was to evaluate the possible protective effects of Urtica dioica (UD) against liver damage in the common bile duct-ligated rats. A total of 24 male Sprague Dawley rats were divided into three groups, namely, control, bile duct ligation (BDL) and BDL + received UD groups, containing eight animals in each group. The rats in UD-treated groups were given UD oils (2 ml/kg) once a day intraperitoneally for 2 weeks starting 3 days prior to BDL operation. The change demonstrating the bile duct proliferation and fibrosis in expanded portal tracts includes the extension of proliferated bile ducts into the lobules; inflammatory cell infiltration into the widened portal areas were observed in BDL group. Treatment of BDL with UD attenuated alterations in liver histology. The α-smooth muscle actin, cytokeratin-positive ductular proliferation and the activity of terminal deoxynucleotidyl transferase dUTP nick end labeling in the BDL were observed to be reduced with the UD treatment. The data indicate that UD attenuates BDL-induced cholestatic liver injury, bile duct proliferation and fibrosis.
Airway inflammation and related respiratory complaints are common symptoms among waste management workers (WMWs). This study investigated the relationship between exposure to municipal solid waste (MSW) and the levels of inflammatory markers and oxidative stress among WMW of Ogun State, South West Nigeria. A total of 280 subjects consisting of 180 WMW and 100 controls were recruited. Ten millilitres of blood were collected from antecubital vein of the subjects for analysis. Results reveal that exposure to MSW is associated with systemic inflammation and oxidative stress. Significant (p < 0.001) elevation of ceruloplasmin (Cp) and C-reactive protein was associated with marked decreases in superoxide dismutase (p < 0.01), catalase (p < 0.001), and glutathione (p < 0.05) and significant (p < 0.001) increases in malondialdehyde (MDA) and uric acid when compared with control. Haematological disorders include significant (p < 0.05) decreases in haemoglobin, packed cell volume, and mean corpuscular volume and significant (p < 0.01) increase in total leucocyte count. Apart from decreased albumin (p < 0.05) and elevated aspartate aminotransferase (p < 0.05) activity observed in WMW, other markers of hepatic (alanine aminotransferase, alkaline phosphatase, total cholesterol and triglycerides) and renal (urea and creatinine) functions did not change significantly (p > 0.05) when compared with the control. A positive correlation between leucocytes (r = 0.195, p < 0.01), Cp (r = 0.210, p < 0.01) and job duration and between Cp and MDA (r = 0.200, p < 0.01) and Cp and leucocytes (r = 0.260, p < 0.001) were observed in WMW. Overall, exposure to MSW predisposes to systemic inflammation and oxidative stress and Cp may be a useful biomarker for monitoring health status of Nigerian WMWs.
In this study, the effects of gilaburu (Viburnum opulus) juice on colon tumorogenesis were investigated. Eight weeks old Balb-C male mice received subcutaneous injections of 1,2-dimethylhydrazine (DMH) (20 mg/kg body weight) once a week for 12 weeks. Both the sham control (group 1) and the DMH control (group 2) groups received drinking water alone, whereas the mice of groups 3 and 4 received gilaburu juice for 30 weeks (started with first DMH injection) and for 18 weeks (started after last DMH injection), respectively. Eighteen weeks after the last DMH injection, all mice were killed and the histogenesis of colon tumors was investigated from the paraffin-embedded sections of colon, which were stained with hematoxylin–eosin. The sites and incidences of tumoral lesions (low-grade dysplasia, high-grade dysplasia, intramucosal carcinoma and invasive carcinoma) were analyzed and compared with control. The results showed that the body weights of the mice were similar in all the groups. No tumoral lesions were found in group 1. Colon tumors developed in all DMH-treated mice (groups 2, 3 and 4). In these groups, the greatest numbers of tumor lesions were detected in the distal colon, followed by the mid-colon and only a few in the proximal colon. There was a reduction in the mean total number of tumor lesion in groups 3 (8.5) and 4 (8.3), when compared to group 2 (11.3). The incidence of invasive carcinoma in group 3 was significantly lower than group 2 (p < 0.05). On the basis of these results, we conclude that gilaburu juice may be useful for the prevention of colon cancer at the initiation stage.
The aim of this study is to measure the alterations in the trace levels of serum copper (Cu), selenium (Se), and manganese (Mn) in forestry workers testing immunoglobulin G (IgG)-positive for Brucella, Borrelia, and Rickettsia. The study was conducted on a sample of 758 subjects (560 male and 198 female). All the subjects underwent medical examinations, which investigated particularly the presence of clinical signs compatible with zoonoses, and routine blood tests from venous blood sample, which tested previous immunisation versus cited microorganisms and serum concentration of Cu, Se, and Mn. The subjects were divided according to IgG positivity versus the cited microorganisms. The group of subjects with IgG positive versus Brucella showed statistically significant higher Cu levels than controls, while the Mn levels were not; the group of subjects with IgG positive versus Rickettsia showed higher levels of all three tested metals. The concentration of the examined metals did not show statistically significant difference between IgG-positive subjects versus subjects with Borrelia compared to controls. These data could confirm the role of both Cu and Se in the regulation of immune response.
Breast milk contains both essential and nonessential trace elements. Mercury, cadmium and lead are nonessential, potentially toxic heavy metals with hematotoxic, neurotoxic and nephrotoxic properties even at very low concentrations. The objectives of this study were to determine the concentrations of mercury, cadmium and lead in the breast milk of healthy lactating women who were living in Isfahan, Iran. Concentrations of mercury, cadmium and lead were determined by graphite furnace atomic absorption spectrometry in 37 milk samples from healthy lactating women collected on first to sixth postpartum week. Accuracy of the analysis was checked by various methods including the use of reference material. The mean ± SD of the concentrations of mercury, cadmium and lead in human milk were 0.92 ± 0.54 μg/L (range 0.0–2.07 μg/L), 1.92 ± 1.04 μg/L (range 0.45–5.87 μg/L) and 7.11 ± 3.96 μg/L (range 3.06–19.47 μg/L), respectively. The results of this study showed that the concentrations of mercury, lead and cadmium in the milk samples from lactating women in Isfahan were high, which makes a major public health hazard for the inhabitants, especially neonatal and children, of the industrial locations. The results of the present study indicate a need for establishing safe intake values of heavy metals in human milk.
Single-cell protein (SCP) refers to the dried cells of microorganisms. The aim of this research was to evaluate the nutrional characteristics and possible toxic effects of the SCP of Trichoderma harzianum. First, T. harzianum was grown on whey filtrate agar medium and the obtained SCP was analysed. It was rich in both total protein (34.21%) and ash (4.78%). Furthermore, the biomass contained all the essential amino acids, and the amino acid concentrations were very close to the FAO reference protein levels. Second, we exposed zebrafish (Danio rerio) embryos to diluted SCP at various concentrations for 96 hours postfertilization (hpf). Compared with the control group, we did not observe any developmental abnormalities, delayed hatching, and lethal effects on zebrafish embryos (96 hpf) found in the SCP group. To test diet effects on spawning success and growth of embryos, adult zebrafish were fed on SCP and flake feed diets for 10 weeks. The number of laid eggs, wet weight and diameter of eggs, and the percentages of hatched eggs from fish fed the flake diet and SCP diet were not significantly different from each other. Also, larval length and weight were not significantly affected by diets. Finally, SCP did not cause any toxic effect on zebrafish adults and their offsprings and could be useful as fish food or food additive.
Fenpyroximate (FP), an acaricide, is widely used in the prevention of acarids (mites) in fruit plant gardens. In this study, the acute toxic effects of different concentrations of FP were investigated using adult guppy (Poecilia reticulata Peters, 1859). Guppy adults were exposed to a range of FP concentrations (25, 50, 75, 100, 125, and 150 µg/L) during 48 h. Static method, which is one of the acute toxicity experiments, has been used in this study. According to probit analysis, the 48-h median lethal concentration (LC50) value of FP at 26°C was found to be 72.821 µg/L. Sublethal exposures were predetermined based on 48-h LC50 value. Guppies were exposed to low concentrations (15, 25, and 50 µg/L) of FP for 48 h. Signs of paralysis and behavior deformations were monitored every 12 h in a number of live and dead adults. Low concentrations of FP were also responsible for erratic swimming, loss of equilibrium, and being lethargic. Liver histology revealed several pathological damages including congestion, picnotic nucleus, sinusoidal dilatation, increase in melanomacrophagic centers, and endothelial degeneration. Finally, the toxicity test results provided 48-h LC50 value for FP, and low concentrations of FP can be highly detrimental to guppy adults with clear evidence of behavioral and histologic effects.
Schistosomiasis is one of the major human parasitic diseases in many developing countries and is one of the causes of morbidity and mortality in the human population. The present work has been planned to study the histopathological and immunohistochemical expression of P53 and CD68 in mouse liver tissues experimentally infected with Schistosoma mansoni, in addition to the ameliorating role of silymarin. A total of 50 adult male mice were divided into 5 groups (10 animals each). Groups 1 and 2 were the control and silymarin groups, respectively, while group 3 was the infected group in which the mice were infected with S. mansoni live cercariae for 6 weeks. Groups 4 and 5 were the cotreated and posttreated groups, respectively, in which mice were infected with cercariae of S. mansoni and treated with silymarin during and after Schistosoma infection, respectively. The major histopathological lesions were variable numbers of perioval granulomas, diffuse infiltration of inflammatory cells, mainly eosinophils and small mononuclear cells, and fibrosis of portal areas and interlobular septa. Treatment with silymarin led to a significant reduction in granuloma area in all treated infected mice compared with nontreated infected mice. Immunohistochemical observations of the liver tissues showed a significant increase in the apoptotic proteins P53 and CD68 after the infection with the cercariae of Schistosoma, compared with the control group. The expression of the cytoplasmic P53 and CD68 was very low in the control liver sections. A significant decrease in the expression of the cytoplasmic P53 and CD68 was observed after silymarin treatment.
The urban green space and environment should be considered to be among the most fundamental elements of the sustainability of natural and human life in the new citizenship. To investigate the effect of irrigation on northern Mashad municipal effluent treatment plant effluent on the chemical properties of soil and accumulation of nutrient in poplar trees, a study was carried out using a random–systematic pattern. To investigate soil as well as accumulation of nutrients and cadmium in leaves, samples of soil (0–20, 20–40 and 40–60 cm) and leaves were taken from each plot in four replications. The measurements carried out in the laboratory showed that the cadmium of the samples of leaf and soil in the compound irrigated with waste water was significantly more than the compound irrigated with well water. The results of the present research suggest that urban waste water can be used as a source of irrigation whereas muck can be employed in forestation and irrigation with precise and particular supervision and control.
Utilization of migratory locusts (Locusta migratoria) as a main substrate due to its high protein content for inulinase (2,1-β-<sc>d</sc>-fructan fructanohydrolase) production by Geotrichum candidum OC-7 was investigated in this study. To optimize fermentation conditions, four influential factors (locust powder (LP) concentration, sucrose concentration, pH and fermentation time) at three levels were investigated using Taguchi orthogonal array (OA) design of experiment (DOE). Inulinase yield obtained from the designed experiments with regard to Taguchi L9 OA was processed with Minitab 15 software at ‘larger is better’ as quality character. The results showed that optimal fermentation conditions determined as LP 30 g/l, sucrose 20 g/l, pH 6.0 and time 48 h. Maximum inulinase activity was recorded as 30.12 U/ml, which was closer to the predicted value (30.56 U/ml). To verify the results, analysis of variance test was employed. LP had the greatest contribution (71.96%) among the other factors. Sucrose had lower contribution (13.96%) than LP. This result demonstrated that LP had a strong effect on inulinase activity and can be used for enzyme production. Taguchi DOE application enhanced enzyme activity to about 3.05-fold versus unoptimized condition and 2.34-fold versus control medium. Consequently, higher inulinase production can be achieved by the utilization of an edible insect material as an alternative substrate and Taguchi DOE presents suitable optimization method for biotechnological process.
2,3,7,8-Tetracholorodibenzo-p-dioxin (TCDD) is a highly toxic environmental contaminant that causes severe toxic effects in animal and human. In this study, we investigated the toxic effects of TCDD and the preventive effects of protocatechuic acid (PCA), a widespread phenolic compound, in the heart tissue of rats. For this purpose, 3–4 months old 28 rats with 280–310 g body weights were equally divided into 4 groups (control, TCDD, PCA, TCDD + PCA group). A 2 μg/kg dose of 2,3,7,8-TCDD and 100 mg/kg dose of PCA were dissolved in corn oil and given orally to the rats for 45 days. The results indicated that TCDD induced oxidative stress by increasing the level of thiobarbituric acid reactive substance and by decreasing the levels of glutathione, catalase, glutathione peroxidase and superoxide dismutase in the heart tissue of rats. In contrast, PCA treatment prevents the toxic effects of TCDD on oxidative stress. In addition, histopathological alterations such as necrosis and hemorrhage occurred in TCDD group, and PCA treatment partially prevents these alterations in heart tissue. In this study, it was concluded that TCDD exposure led to toxic effects in heart tissue and PCA treatment could prevent the toxicity of TCDD.
In this study, the toxicity, behavioural and regeneration effects of dimethylformamide (DMF) on planarian Dugesia japonica were investigated. One control and six different concentrations of DMF (10 ppm, 100 ppm, 500 ppm, 1000 ppm, 5000 ppm and 10,000 ppm) were used in triplicate. The results showed that the mortality was directly proportional to the DMF concentration and planarian locomotor velocity (pLMV) was significantly reduced by increasing the exposure time and DMF concentration. pLMV of D. japonica was significantly reduced at a lower concentration of 10 ppm after 7 days of continuous exposure to DMF. The recovery of the motility of planarians pretreated with DMF was found to be time- and dose dependent, all planarians had complete recovery in their motility after 48 h. The appearance of auricles in regenerating animals was easily affected by DMF exposure in comparison with the appearance of eyespot. The present results suggest that the intact adult mobility in the aquatic planarian D. japonica is a more sensitive biomarker than mortality, and the appearance of auricles in regenerating animals is a more sensitive biomarker than eyespot.
This study was carried out to evaluate the protective role of borax (BX) on genotoxicity induced by aluminum (Al) in rat liver, using liver micronucleus assay as an indicator of genotoxicity. Sprague-Dawley rats were randomly separated into six groups and each group had four animals. Aluminum chloride (AlCl3; 5 mg/kg b.w.) and BX (3.25 and 13 mg/kg b.w.) were injected intraperitoneally to rats. Besides, animals were also treated with Al for 4 consecutive days followed by BX for 10 days. Rats were anesthetized after Al and BX injections and the hepatocytes were isolated for counting the number of micronucleated hepatocytes (MNHEPs). AlCl3 was found to significantly (p < 0.05) increase the number of MNHEPs. Rats treated with BX, however, showed no increase in MNHEPs. Moreover, simultaneous treatments with BX significantly modulated the genotoxic effects of AlCl3 in rats. It can be concluded that BX has beneficial influences and has the ability to antagonize Al toxicity.
Paraquat (PQ) is a potent toxicant for humans, and poisoning with PQ is associated with high mortality. Patients with severe PQ-induced poisoning may die of multiple organ failure involving the circulatory and respiratory systems. Death resulting from epilepsy-like convulsions, which are infrequently noted reported with PQ poisoning, is observed clinically with this condition. This study presents the clinical data of five patients with severe PQ-induced poisoning who died of epilepsy-like convulsions, and related publications were reviewed in order to investigate the pathogenesis, clinical manifestations, and prognosis of these convulsions. Our results may help prevent this event and improve the success of treatment.
The aim of this study was to investigate the possible oxidative stress and the antioxidant response, which were caused on maize by boron (B). For this, 11- and 15-day-old maize seedlings were subjected to 2 or 4 mM B in the form of boric acid (H3BO3) for 2 and/or 6 days. At the end of the treatment period, root length, hydrogen peroxide (H2O2) content, malondialdehyde (MDA) content and the antioxidant enzymes superoxide dismutase (SOD), peroxidase (POX) and catalase (CAT) were measured. The results revealed that root length of plants, activity of antioxidative enzymes such as SOD, POX and CAT and also H2O2 contents and MDA levels were seriously affected by excess B. These results suggested that the oxidative stress occurred due to the toxic effect of B.
The aim of this study is to investigate the acute toxic effects of high-dose toluene and its mechanisms on the liver tissue of toluene-treated rats. In this study, 16 adult male Wistar albino rats (200–220 g) were divided into two equal groups. Group I was used as a control group, while group II was exposed to high dose of toluene, 5200 mg/kg (6 ml/kg per gavage). After the 3-hour experimental period, blood samples and liver tissues were taken from the euthanized animals. Serum aspartate and alanine aminotransferase levels were assayed. Liver tissues were fixed in 10% neutral formalin, then embedded in paraffin and sectioned (5 μm thickness). Sections were stained with hematoxylin and eosin for histopathological examination. A terminal transferase dUTP nick end labeling assay was also done for the determination of apoptosis in liver tissues. For the determination of Bax and caspase-3 immunoreactivity, the sections were stained using avidin–biotin–peroxidase immunohistochemical method. The level of plasma transaminase was found to be increased in toluene administered rats. Additionally, slight degeneration of hepatocyte and mononuclear cell infiltration was observed in the liver tissue sections and a high (+++) immunoreactivity for Bax and caspase-3 protein was observed in the toluene group. This study showed that the high dose of toluene triggers apoptosis in the liver of rats via the mitochondrial pathway in acute period.
Oxidative stress is accepted as a potential responsible mechanism in the pathogenesis of radiocontrast media (RCM)-induced hepatotoxicity. Therefore, we aimed to investigate the protective effects of ebselen against RCM-induced hepatotoxicity by measuring tissue oxidant/antioxidant parameters and histological changes in rats. Wistar albino rats were randomly separated into four groups consisting of eight rats per group. Normal saline was given to the rats in control group (group 1). RCM was given to the rats in group 2, and both RCM and ebselen were given to the rats in group 3. Only ebselen was given to the rats in group 4. Liver sections of the killed animals were analyzed to measure the levels of malondialdehyde (MDA) and activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), as well as histopathological changes. In RCM group, SOD and CAT levels were found increased. In RCM-ebselen group, MDA, SOD and CAT levels were found decreased. In RCM-ebselen group, however, GSH-Px activities of liver tissue increased. All these results indicated that ebselen produced a protective mechanism against RCM-induced hepatotoxicity and took part in oxidative stress.
Almost 2555–4380 tons of paint sludge are produced annually in an auto-manufacturing plant; recycling and reproduction of beneficial materials such as titanium dioxide (TiO2) and its application in paint production from paint sludge are evaluated in this article. The disposal of these sludge is environmentally important and is the main and most serious challenge for auto-manufacturing units. Today, these sludge are recognized as toxic wastes, whose disposal is much costly and constrained by environmental standards. Controlled disposal requires spaces, which are expensive and impermeable, because the sludge contains large amounts of hazardous materials such as heavy metals, solvents, and other materials polluting wells, springs, and other water resources. In this research, X-ray diffraction spectroscopy was carried out to determine the types of sludge combinations. Then, chemical digestion and centrifuge was used to extract TiO2, the extracted TiO2 reached 67.41% using these techniques. Next, a powder containing TiO2 in a certain percentage was used for paint production. Here, not only the amount of sludge decreased to as much as 70% but also the fresh paint required annually will be reduced by 21%. Furthermore, all heavy metals and toxic wastes will be removed as an environmental challenge.
Aluminium (Al) is used in water purification and is also present in several manufactured foods and medicines. Al is known to induce a broad range of physiological, biochemical and behavioural dysfunctions in laboratory animals and humans. This investigation was carried out to investigate the effects of subchronic exposure to Al (as AlCl3) in rats. Sprague-Dawley rats were randomly separated into two groups. Group 1 rats treated with sodium chloride served as the control, group 2 rats were treated with Al (as AlCl3, 5 mg/kg body weight) intraperitonally for 10 weeks. Animals were killed and blood samples were analyzed for blood serum alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) enzyme activities and creatinine, urea (U) and uric acid (UA) levels for evaluating hepatotoxicity and nephrotoxicity. Blood parameters including red blood cells (RBCs), haemoglobin (Hb) concentration, haematocrit (Ht), platelets (PLTs) and white blood cells (WBCs) were compared between control and experimental group to assess haematoxicity. In order to determine the genotoxicity, the number of micronucleated hepatocytes (MNHEPs) was counted in isolated hepatocytes. In addition, histological alterations in liver and kidney samples were investigated. After exposure with Al, the enzymatic activities of ALP, AST, ALT and LDH, and the levels of U and UA significantly increased. RBC, WBC, PLT, Hb and Ht revealed significant decreases in experimental group compared to the control. AlCl3 caused a significant increase in MNHEPs. Furthermore, severe pathological damages were established in both liver and kidney samples. Subchronic exposure to low doses of Al can produce serious dysfunctions in rat blood, liver and kidney, and exposure to this metal can result in greater damages.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces hepatic damage. Propolis exhibits antioxidant properties and several studies suggest that supplementations with antioxidants can influence hepatotoxicity. Therefore, the aim of the current study was to explore the effectiveness of propolis in alleviating the toxicity of TCDD in the liver of rats. Animals were divided into six groups, namely, TCDD (0.75 and 8 µg/kg body weight (bw)), propolis (50 mg/kg bw), TCDD (0.75 and 8 µg) plus propolis (50 mg/kg bw), and control, respectively. Rats were intraperitoneally administered with their respective doses daily for 21 days. In rats that received a high dose of TCDD, the antioxidant enzymes were significantly decreased and the serious pathological findings were established. Also, the rate of hepatocyte micronucleus (HMN) was increased after treating with TCDD. The reactions of enzymes in control and low-dose group were weak. The frequencies of HMN and liver histology were similar to both the groups. The presence of propolis with TCDD alleviated its pathological effects in hepatic tissue. Propolis also prevented the suppression of antioxidant enzymes in the livers of animals exposed to TCDD and displayed a strong protective effect against HMN. It can be concluded that propolis has beneficial influences and was able to antagonize TCDD toxicity in the liver.
The effect of different periods of lead exposure on deficits of learning and memory is still unclear. In this study, we conduct in vivo experiment to investigate the critical stages when lead induced neurotoxicity in rats and its underlying mechanisms in some critical stages. Rats were exposed to 0.2% mg/ml lead acetate solution via drinking water during gestation, lactation and ablactation periods. Behavior deficits were found in gestation and lactation. N-Methyl-<sc>d</sc>-aspartate (NMDA) receptor subunit 2A (NR2A) increased during gestation both in hippocampus and cerebral cortex compared to the control group; in all treatment groups NR2B decreased in hippocampus and in cerebral cortex during the lactation period. Meanwhile, in hippocampus metabotropic glutamate receptor 1 (mGluR1) decreased during gestation and lactation periods but increased during the ablactation period. These observations suggest that exposure to lead in gestation and lactation periods could cause neurobehavioral deficits which extend to adulthood, and lactation was a more sensitive period for lead exposure. Furthermore, the abnormal expression of NMDA receptor 2 (NMDAR 2) subunits and mGluR1 are likely to be associated with the impairment.