Effects of atorvastatin and carvedilol on chronic cyclosporine nephrotoxicity in rats

Effects of Atorvastatin and Carvedilol on chronic Cyclosporine nephrotoxicity in rats.Cyclosporine (CsA) is widely used in the treatment of autoimmune diseases and transplantation, an immunosuppressive agent. Despite the therapeutic benefit provided by the use of CsA, in clinical usage with the large number transplant and other groups of patients, side-effects (nephrotoxicity, neurotoxicity, hepatotoxicity, hypertension, dyslipidemia, cosmetic problems, malignancy, and an increase in cardiovascular events) also have been reported. The most important of these side effects is chronic CsA nephrotoxicity. Chronic CsA nephrotoxicity is associated with irreversible histological damage in renal arterioles, tubulointertisyel tissue and glomerules. Clinically, this injury results in progressive renal dysfunction. In some cases, end-stage renal failure can be developed. Therefore, prevention of this toxicity is of great importance. Pharmacological agents have also been proposed in addition to discontinuation of cyclosporine and reducing the dose in order to prevention of chronic CsA nephropathy. Our aim is to eveluate of the chronic usage of CsA biochemical and histopathological renal functions, free oxygen radicals by renal tissue, antioxidant enzymes, osteopontin and NO levels, also to determine the effects of chronic therapy with carvedilol and atorvastatin separately and in combination on biochemical and the histopathologic level renal functions, and to ivenstigate the possible protective effects of theese therapies on free oxygen radicals, antioxidant enzymes, osteopontin and NO levels.30 adult male Wistar albino rats weighing 200-250 grams were included. The subjects were randomized to each group of six rats were divided into 5 groups. The first group (control group) 2 ml of saline, 2 group are (CsA group) 25 mg/kg/day CsA, 3 group are (CsA + Carvedilol group) 25 mg/kg/day CsA and 4 mg/kg carvedilol, 4 group are (CsA + atorvastatin group) 25 mg/kg/day CsA and 10 mg/kg atorvastatin, 5 group are (CsA + Carvedilol + atorvastatin group) 25 mg/kg/day CsA, 4 mg/kg carvedilol and 10.mg/kg atorvastatin was subcutaneously administered for 21 days. All subjects? serum blood urea nitrogen (BUN) and creatinine levels were measured. Creatinine clearance was calculated. Renal tissue MDA, SOD, NO levels were measured. Histopathologic evaluation was performed. The presence of osteopotin was evaluated by immunohistochemistry.As a result of our study atorvastatin and carvedilol treatments were found to be protective against chronic CsA nephropathy at the level of both the biochemical and histopathological. These agents also decrease the proinflamatuar and oxidant parameters of renal tissue and increased NO level.Key words: Cyclosporine nephrotoxicity, Atorvastatin, Carvedilol