Targeting superoxide dismutase to renal proximal tubule cells inhibits nephrotoxicity of cisplatin and increases the survival of cancer-bearing mice.
Because cis-diamminedichloroplatinum(II) (cisplatin) which generates reactive oxygen species induces renal dysfunction, administration of a large dose for killing cancer cells is highly limited. We recently synthesized a cationic superoxide dismutase (SOD) (hexamethylenediamine-conjugated SOD, AH-SOD) which rapidly accumulates in renal proximal tubule cells and inhibits oxidative injury of the kidney. Treatment of Ehrlich ascites tumor cells (EATC)-bearing mice with cisplatin sufficient for killing tumor cells increased their motality. The motality of cisplatin-treated EATC-bearing mice was markedly decreased by AH-SOD. These results suggest that targeting SOD to renal proximal tubule cells might permit the administration of high doses of cisplatin and related anticancer agents without causing renal injury.
Nishikawa
M
M
Department of Biochemistry, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka, Japan. nishikawa@med.osaka-cu.ac.jp
Nagatomi
H
H
Nishijima
M
M
Ohira
G
G
Chang
B J
BJ
Sato
E
E
Inoue
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D002945:Cisplatin / Q000009:adverse effects* / Q000494:pharmacology; D003959:Diamines / Q000008:administration & dosage / Q000493:pharmacokinetics; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D013482:Superoxide Dismutase / Q000008:administration & dosage* / Q000493:pharmacokinetics
D000970:Antineoplastic Agents; D003959:Diamines; D013482:Superoxide Dismutase; D002945:Cisplatin; C007297:1,6-diaminohexane