Sildenafil protects against nitric oxide deficiency-related nephrotoxicity in cyclosporine A treated rats

摘要: Abstract Cyclosporine A (CsA) is the most widely used immunosuppressant in organ transplant surgery and treatment of autoimmune disease. Nevertheless, animal clinical studies have demonstrated that nephrotoxicity major adverse effect limiting prolonged CsA therapeutic use. The present study aimed to investigate possible protective sildenafil, a phoshodiestrase-5 inhibitor, on CsA-induced various mechanism(s) underlies this effect. Male Wistar rats were administered (20 mg/kg/day, s.c.) for 21 days alone or combination with sildenafil (5 mg/kg/day, p.o.). Sildenafil exhibited nephroprotective effects as evidenced by significant decrease serum creatinine urea levels, spot urine albumin–creatinine ratio, well levels renal malondialdehyde nitric oxide, concurrent increase level reduced glutathione catalase activity compared CsA-treated rats. Additionally, immunohistochemical analysis markedly inducible oxide synthase, tumor necrosis factor-alpha, caspase-3 expressions, while expression endothelial synthase was prominently enhanced. confirmed histopathological examination. Pretreatment l -nitro-arginine methyl ester (10 mg/kg/day, i.p.), non-selective reversed protection afforded sildenafil. Taken together, current highlighted renoprotective against rats, which might be mediated, part, through pathway antioxidant, anti-inflammatory, anti-apoptotic activities.