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Activation of nuclear factor erythroid 2‐related factor 2 (Nrf2) and Nrf‐2‐dependent genes by ischaemic pre‐conditioning and post‐conditioning: new adaptive endogenous protective responses against renal ischaemia/reperfusion injury

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Acta Physiologica

Published online on

Abstract

Aim To investigate the impact of ischaemic pre‐conditioning (Ipre) and post‐conditioning (Ipost) on expression of nuclear factor erythroid 2‐related factor 2 (Nrf2) gene and its dependent genes, haem oxygenase‐1 (HO‐1) and NADPH‐quinone oxidoreductase‐1 (NQO‐1); inflammatory cytokines TNF‐α, IL1β and ICAM‐1; and apoptotic markers such as caspase‐3 in renal ischaemia/reperfusion (I/R) injury. Methods One hundred and fifty male Sprague Dawley rats were classified into five groups (each consisted of 30 rats): sham, control (I/R), Ipre + I/R, Ipre without I/R and Ipost + I/R. Serum creatinine and blood urea nitrogen (BUN) were measured at 2, 24 and 48 h after ischaemia. In kidney tissues, mRNA of Nrf2, HO‐1, NQO‐1, TNF‐α, IL‐1β and ICAM‐1 and immunohistochemical expression of Nrf2 and caspase‐3 were assessed. Results Serum creatinine and BUN improved significantly in Pre + I/R group; however, they did not show any significant improvement in Post + I/R group. Also, Ipre‐I/R group showed non‐significant change in serum creatinine and BUN. The expression of Nrf2, HO‐1 and NQO‐1 is increased significantly in Pre + I/R and Pre − I/R groups, while the enhancement in Post + I/R group was non‐significant. Moreover, the expression of proinflammatory cytokines (TNF‐α, IL‐1 and ICAM‐1) and apoptotic (caspase‐3) markers showed high significant attenuation in Pre + I/R group, but slight significant attenuation in Pre + I/R group. Conclusion The renoprotective action of Ipre might include early activation and enhanced expression of Nrf2 gene and its dependent antioxidant genes, HO‐1 and NOQ1, as endogenous adaptive renoprotective genes, as well as reduction in TNF‐α, IL‐1β, ICAM‐1 and caspase‐3.