Effect of colchicine on cyclosporine nephrotoxicity, reduction of TGF-beta overexpression, apoptosis, and oxidative damage: An experimental animal study

PubMedID: 15251335Background Proinflamatory and profibrotic cytokines may be responsible for the cyclosporine A nephrotoxicity. Increased levels of apoptosis, free oxygen redicals, and transforming growth factor beta (TGF-ß), may play an important roles in the pathogenesis of nephrotoxicity. In this experimental animal study, we sought to investigate the effects of colchicine on the cyclosporine nephrotoxicity. Method Twenty-four Wistar albino rats were divided into three groups: cyclosporine 15 mg/kg subcutaneously (SC); cyclosporine 15 mg/kg SC plus colchicine 30 mcg/kg orally; and a control group; equal doses of olive oil orally were administered to groups 1, 2, and 3. Renal function, cyclosporine levels, and serum malonyldialdehyde (MDA) levels were measured at the end of 4 weeks. Apoptosis, TGF-ß, and other findings were detected in renal tissue with the TUNEL method, with a immunohistochemical method, and with routine staining procedures, respectively. Results There were significant differences in the values of mean creatinine clearance between group 1 and group 3 and between group 2 and group 3 (P .05). MDA levels in group 1 were high compared with the control group (P .05). Renal tubular vacuolization in group 1 and group 2 animal were greater than in the control group, but no significant difference were observed between any of the groups (P > .05). Mononuclear cell infiltration in group 1 and group 2 hosts were higher than the control group, but there was no significant differences between the groups (P > .05). Afferent arteriolar hyalinization was observed group 1 and 2 but not group 3. There was a statistically significant difference between group 1 and group 3 and between group 2 and group 3 (P .05). Apoptotic cell death count of group 1 was higher than that in group 2 or group 3 (P < .05, for each comparison); moreover, group 2 also showed greater numbers of apoptotic cells than group 3 (P < .001). At the end of the 4 weeks, there was no intersititial fibrosis in any of the hosts. Conclusion While cyclosporine caused increased TGF-ß expression and apoptotic cell death in the renal tissue of rats colchicine prevented the increase in MDA serum levels, TGF-ß expression, and apoptosis in renal tissue. Our study suggests that colchicine may diminish the cyclosporine nephrotoxicity by its suppressing the expression of TGF-ß, apoptotic cell death, and MDA production