title: Targeting superoxide dismutase to renal proximal tubule cells inhibits nephrotoxicity of cisplatin and increases the survival of cancer-bearing mice.
abstract: 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.
authors.affiliation: Department of Biochemistry, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka, Japan. nishikawa@med.osaka-cu.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Nishikawa
authors.forename: H
authors.initials: H
authors.lastname: Nagatomi
authors.forename: M
authors.initials: M
authors.lastname: Nishijima
authors.forename: G
authors.initials: G
authors.lastname: Ohira
authors.forename: B J
authors.initials: BJ
authors.lastname: Chang
authors.forename: E
authors.initials: E
authors.lastname: Sato
authors.forename: M
authors.initials: M
authors.lastname: Inoue
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D003959:Diamines; D013482:Superoxide Dismutase; D002945:Cisplatin; C007297:1,6-diaminohexane