Polyoxyethylene-modified superoxide dismutase reduces side effects of adriamycin and mitomycin C.
Polyoxyethylene-modified superoxide dismutase (SOD-POE) is a newly developed long-acting superoxide dismutase. Adriamycin (ADR) and mitomycin C (MMC) generate superoxide, which contributes to their cytocidal effects or side effects. We examined whether SOD-POE could prevent the side effects induced by superoxide generated by antitumor agents, and the following results were obtained. SOD-POE did not influence the antitumor effects of ADR and MMC either in vitro or in vivo, but prevented the toxic death of BALB/c, nu/nu male mice caused by overdoses of ADR or MMC. As for its effective sites, SOD-POE prevented a decrease in the specific activity of rotenone-sensitive NADH-ubiquinone oxido-reductase (complex I) in heart muscle mitochondrial respiratory chain function in BALB/c male mice administered 10 mg/kg ADR, and prevented damage to the sarcoplasmic reticulum and mitochondria of mouse heart muscle by ADR as observed by electron microscopy. Furthermore, SOD-POE prevented bone marrow suppression induced by MMC in Donryu rats. The above results suggest that combination chemotherapy with SOD-POE would make it possible to increase the maximum permissible doses of antitumor agents, improving the efficacy of these agents.
Kawasaki
S
S
Department of Surgery II, Nagoya University School of Medicine.
Akiyama
S
S
Kurokawa
T
T
Kataoka
M
M
Dohmitsu
K
K
Kondoh
K
K
Yamauchi
M
M
Ito
K
K
Watanabe
T
T
Sugiyama
S
S
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D004317:Doxorubicin / Q000494:pharmacology / Q000633:toxicity*; D004354:Drug Screening Assays, Antitumor; D004579:Electron Transport / Q000187:drug effects*; D004938:Esophageal Neoplasms / Q000188:drug therapy*; D006321:Heart / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology*; D016685:Mitomycin / Q000494:pharmacology / Q000633:toxicity*; D009206:Myocardium / Q000473:pathology* / Q000648:ultrastructure; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D009368:Neoplasm Transplantation; D011092:Polyethylene Glycols / Q000494:pharmacology*; D012402:Rotenone / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D012402:Rotenone; D011092:Polyethylene Glycols; D016685:Mitomycin; D004317:Doxorubicin; D013482:Superoxide Dismutase; C077064:polyoxyethylene-superoxide dismutase; D016660:NAD(P)H Dehydrogenase (Quinone)