Effects of Atorvastatin and Carvedilol on Chronic Cyclosporine Nephrotoxicity in Rats

Abstract

Background: To evaluate possible renoprotective effects of carvedilol and atorvastatin in CsA induced kidney injury in a rat model. Methods: Twenty-two rats were divided into five groups. Control, CsA, CsA+karvedilol, CsA+Atorvastatin, CsA +karvedilol+atorvastatin groups. Drugs were given for 21 days. Results: Serum BUN and creatinine were significantly higher in the CsA group compared to control and were significantly lower in the CsA+carvedilol+atorvastatin group compared to CsA group. Tissue MDA levels were found to be lower in group 3, 4 and 5 than in CsA group. Tissue SOD in CsA +carvedilol and CsA+atorvastatin groups were found higher than the control and CsA groups. Tissue NO levels were found to be higher only in CsA+carvedilol+atorvastatin group compared to CsA group. Apical budding, hyaline casts and apoptosis in the tubular system was significantly higher in the CsA group than in the treatment groups. Osteopontin showed strong positivity especially in the CsA group. Osteopontin density was lower in the treatment group. Conclusions: This is the first study to evaluate MDA, SOD and NO at tissue level for carvedilol in cyclosporine nephrotoxicity. Carvedilol and atorvastatin may contribute to the reduction of renal injury in chronic CsA nehropathy. These agents have provided a protective effect on renal functions especially in combined treatment.