Therapeuticefficacy of naringin on cyclosporine (A) induced nephrotoxicity in rats: Involvement of hemeoxygenase-1

Background: Clinically, chronic nephrotoxicity may lead to renal functional impairment and progress to end stage renal failure. The renoprotective effect of a flavonoid naringin (NG) against cyclosporine A(CsA)-induced nephrotoxicity was investigated in this study. Methods: Nephrotoxicity was induced in male albino Wistar rats by injecting 25 mg/kg body weight of CsA for a period of 21 days. CsA-induced rats were also cotreated with 40 mg of NG/kg body weight, orally. Results: After the experimental period, the levels of lipid peroxides (TBARS) and hydroxyl radical (OH) were found to be elevated, whereas the levels of SOD, catalase, glutathione, vitamin C, E and A were decreased in CsA-induced rats. NG co-treatment signifi-cantly decreased the levels of lipid peroxides and hydroxyl radicals and restored the levels of enzymic and non-enzymic antioxidants in renal tissues. Histological analysis revealed that CsA administration caused severe and widespread necrosis with dilatation of proximal tubules, vacuolization, tubular cell desquamation and intraluminal cast formation with massive infiltration of inflamma-tory cells. CsA-induced histopathological renal changes were minimal in animals which received NG treatment. The western blot and confocal microscopic expression of heme oxygenase-1 was restored by NG. In CsA-induced animals the expression was re-duced compared to NG treated animals. Conclusions: The present study reveals that NG can act as effective renoprotective drug against CsA-induced toxicity. Key words: cyclosporine, naringin, lipid peroxidation, heme oxygenase, nephrotoxicit