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Purpose : To investigate the protective role of genistein against ischemic reperfusion (I/R) injury in rat kidneys. Methods : Group I (control, n = 10) consisted of animals that were not operated on while group II (sham, n = 10) were animals surgically operated on, similar to I/R group without renal bilateral ischemia. Group III (genistein, n = 10) consisted of animals administered 10 mg/kg genistein by oral gavage for 7 consecutive days while group IV (I/R, n = 10) animals were subjected to 45 min of renal bilateral ischemia followed by 24 h of reperfusion. Group V (genistein+I/R, n = 10) received 10 mg/kg genistein by oral gavage for 7 consecutive days and then subjected to 45 min of renal bilateral ischemia followed by 24 h of reperfusion. Renal function, total oxidant capacity and total antioxidant status in serum were evaluated in the rats. Further, reactive oxygen species generation as well as levels of protein carbonyl, lipid peroxidation, and enzymatic and non-enzymatic antioxidants were determined. Nrf-2 (nuclear factor (erythroid-derived 2)-like 2) and HO-1 (Heme oxygenase-1) expressions were determined by western blot. Results : Pre-treatment with genistein (10 mg/kg) significantly (p < 0.001)  ameliorated I/R induced renal damage by reducing the levels of serum markers. Genistein pre-treatment significantly decreased (p <0.001) I/R injury induced-ROS, lipid peroxides and protein carbonyl content (p < 0.001). I/R injury significantly (p < 0.001) decreased non-enzymatic and enzymatic antioxidant activities. Genistein pretreatment also prevented renal I/R injury by significantly up-regulating Nrf-2, HO-1 expressions and antioxidant status. Conclusion : Thus, genistein may be therapeutically useful against kidney I/R injury by improving antioxidant defense mechanisms. Keywords : Oxidative stress, Genistein, Ischemic reperfusion injury, Renal damage, Antioxidant, Nuclear factor (erythroid-derived 2)-like 2, Heme oxygenase-1, Nrf-2, HO-1 Tropical Journal of Pharmaceutical Research is indexed by Science Citation Index

Genistein attenuates ischemia/reperfusion injury in rat kidneys via enhancement of antioxidant defense mechanisms: Activation of Nrf-2/HO-1 signaling