M. Nishikawa et al., Targeting superoxide dismutase to renal proximal tubule cells inhibits mitochondrial injury and renal dysfunction induced by cisplatin, ARCH BIOCH, 387(1), 2001, pp. 78-84
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-diamminedichloropla
tinum(II)elicited oxidative stress in renal mitochondria, decreased the ren
al expression of Bcl-x, released cytochrome c from mitochondria to cytosol,
and induced apoptosis and renal dysfunction by a mechanism that was inhibi
ted 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.