Sildenafil obviates ischemia-reperfusion injury-induced acute kidney injury through peroxisome proliferator-activated receptor γ agonism in rats

Background: Sildenafil is a phosphodiesterase inhibitor used clinically for treating erectile dysfunction. Few studies suggest sildenafil to be a renoprotective agent. The present study investigated the involvement of peroxisome proliferator-activated receptor gamma (PPAR-gamma) in sildenafil-mediated protection against ischemia-reperfusion-induced acute kidney injury (AKI) in rats. Materials and methods: The rats were subjected to ischemia-reperfusion injury (IRI) with 40 min of bilateral renal ischemia followed by reperfusion for 24 h. The renal damage was assessed by measuring creatinine clearance, blood urea nitrogen, plasma uric acid, electrolytes, and microproteinuria in rats. The thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione levels were measured to assess oxidative stress in renal tissues. The hematoxylin-eosin staining was carried out to demonstrate histopathologic changes in renal tissues. Sildenafil (0.5 and 1.0 mg/kg, intraperitoneal) was administered 1 h before subjecting the rats to renal IRI. In a separate group, bisphenol A diglycidyl ether (30 mg/kg, intraperitoneal), a PPAR-gamma receptor antagonist, was given before sildenafil administration followed by IRI. Results: The ischemia-reperfusion demonstrated marked AKI with significant changes in serum and urinary parameters, enhanced oxidative stress, and histopathologic changes in renal tissues. The administration of sildenafil demonstrated significant protection against ischemia-reperfusion-induced AKI. The prior treatment with bisphenol A diglycidyl ether abolished sildenafil-mediated renal protection, thereby confirming involvement of PPAR-gamma agonism in the sildenafil-mediated renoprotective effect. Conclusions: It is concluded that sildenafil protects against ischemia-reperfusion-induced AKI through PPAR-gamma agonism in rats. (C) 2016 Elsevier Inc. All rights reserved.