Colchicine decreases apoptotic cell death in chronic cyclosporine nephrotoxicity

Colchicine has been shown to prevent kidney injury in chronic cyclosporine nephrotoxicity; however, the mechanisms of its action are undetermined. The purpose of this study was to clarity whether colchicine prevents cyclosporine-induced kidney injury by decreasing kidney-cell apoptosis. We also sought to determine whether such an antiapoptotic effect was related to Bcl-2/Bax protein and caspase3 activity. Adult male Sprague-Dawley rats kept on a salt-depleted diet (0.05% sodium) were treated daily for 28 days with cyclosporine (15 mg/kg In 1 mL/kg olive-oil vehicle), colchicine (30 mug/kg In 100% ethanol, diluted with sterile saline solution to a final concentration of 30 mug/mL), or both cyclosporine and colchicine. Kidney function, histomorphologic findings, in situ terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate-biotin nick end-labeling assay, expressions of Bcl-2 and Box proteins, and caspase-3 enzymatic activity were compared for the different treatment groups. Compared with the vehicle-treated rats, rats given cyclosporine showed a decline in creatinine clearance rate, an increase in serum creatinine concentration, tubulointerstitial fibrosis, and an Increase In the number of apoptotic cells (all P < .01). Concomitant administration of colchicine significantly reversed all the above parameters (all P < .05). The decreased expression of Bcl-2 and the ratio of Bcl-2 to Box protein seen In cyclosporine-treated rat kidneys were significantly increased after colchicine treatment, accompanying a suppression of caspase-3 activity (P < .05). Furthermore, the decreased apoptotic cell death was closely correlated with Improved renal tubulointerstitial fibrosis (r = 0.583, P < .05). These findings strongly suggest that a renoprotective effect of colchicine on cyclosporine-induced nephrotoxicity is coassociated with a decrease in apoptotic cells.