Targeting superoxide dismutase to renal proximal tubule cells inhibits mitochondrial injury and renal dysfunction inuduced 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.
Nishikawa
M
M
Department of Biochemistry, Osaka City University Medical School, Japan. nishikawa@med.osaka-cu.ac.jp
Nagatomi
H
H
Chang
B J
BJ
Sato
E
E
Inoue
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002467:Cell Nucleus / Q000473:pathology; D002945:Cisplatin / Q000009:adverse effects*; D053938:DNA Fragmentation; D004272:DNA, Mitochondrial / Q000187:drug effects; D016503:Drug Delivery Systems; D007677:Kidney Function Tests; D007687:Kidney Tubules, Proximal / Q000187:drug effects*; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010101:Oxygen Consumption; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D002945:Cisplatin