Coenzyme Q(10) alleviates tacrolimus-induced mitochondrial dysfunction in kidney

Abstract

The major side effect of tacrolimus (Tac) is nephrotoxicity. We studied whether supplementation of coenzyme Q(10), (CoQ(10)) a potent antioxidant, can reduce Tac-induced nephrotoxicity via improving mitochondrial function. In an in vitro study, CoQ(10) reduced the production of Tac-induced mitochondrial reactive oxygen species and abolished the loss of mitochondrial membrane potential in proximal tubular cell line. Assessment of mitochondrial function revealed that CoQ(10) decreased oxygen consumption and mitochondrial respiration rate increased by Tac, suggesting improvement of mitochondrial function to synthesize ATP with CoQ(10) treatment. The effect of the CoQ(10) in vitro study was observed in an experimental model of chronic Tac-induced nephropathy. CoQ(10) attenuated Tac-induced oxidative stress and was accompanied by function and histologic improvement. On electron microscopy, addition of CoQ(10) increased not only the number but also the volume of mitochondria compared with Tac treatment only. Our data indicate that CoQ(10) improves Tac-induced mitochondrial dysfunction in kidney. Supplementary CoQ(10) treatment may be a promising approach to reduce Tac-induced nephrotoxicity.