Involvement of peroxisome proliferator-eactivated receptor gamma in vitamin D-emediated protection against acute kidney injury in rats

Background: Vitamin D has been reported as renoprotective agents in various studies. Recently, a few in vitro studies highlighted cross talk between vitamin D and peroxisome proliferatoreactivated receptor gamma (PPAR-g). The present study investigated the activation of PPAR-g as novel mechanism in vitamin Demediated protection against ischemia reperfusioneinduced acute kidney injury (AKI) in rats. Materials and methods: The AKI was induced by clamping renal pedicles for 40 min followed by reperfusion for 24 h. The AKI was assessed by measuring creatinine clearance, serum urea, uric acid level, and lactate dehydrogenase activity. Moreover, serum potassium, calcium level, fractional excretion of sodium, and microproteinuria were measured in rats. The oxidative stress in renal tissues was assessed by quantification of thiobarbituric acide reactive substances, superoxide anion generation, reduced glutathione level, and catalase and myeloperoxidase activities. The hematoxylin-eosin staining was carried out to observe histopathologic changes in renal tissues. Vitamin D (0.25, 0.5, and 1 mg/ kg) was administered for 7 d before subjecting rats to renal ischemia reperfusion injury (IRI). Results: The renal IRI in rats induced significant changes in serum, urinary, and oxidative stress parameters in renal tissues. Moreover, hematoxylin-eosin staining revealed marked damage produced by IRI in renal tissues. The administration of vitamin D at 0.5 mg/kg dose afforded maximum protection against renal IRI. The prior treatment with PPAR-g antagonist bisphenol A diglycidyl ether significantly attenuated protective effect of vitamin D, thus confirming involvement of PPAR-g in vitamin Demediated renoprotection. Conclusions: It is concluded that activation of PPAR-g significantly contributes toward vitamin Demediated protection against ischemia reperfusioneinduced AKI. (C) 2013 Elsevier Inc. All rights reserved.