Targeting superoxide dismutase to renal proximal tubule cells inhibits mitochondrial injury and renal dysfunction induced by cisplatin

We recently reported the synthesis of a cationic superoxide dismutase (SOD) derivative (AH-SOD) that rapidly and selectively accumulates in and around proximal tubule cells and effectively dismutes superoxide radicals in situ. The present study revealed that administration of cis-diamminedichloroplatinum(II)elicited oxidative stress in renal mitochondria, decreased the renal expression of Bcl-x, released cytochrome c from mitochondria to cytosol, and induced apoptosis and renal dysfunction by a mechanism that was inhibited by AH-SOD, These results suggest that targeting SOD to proximal tubule cells protects renal function and permits the administration of fairly high doses of nephrotoxic anticancer agents, such as cisplatin, without causing renal injury. (C) 2001 Academic Press.