Polyoxyethylene-modified Superoxide Dismutase Reduces Side Effects of Adriamycin and Mitomycin C

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Abstract
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 oxidoreductase (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.