Influence of dietary manganese and vitamin E on adriamycin toxicity in mice.
Adriamycin (ADR) administration can result in cardiac toxicity. One suggested mechanism of damage is through increased lipid peroxidation. We have evaluated the biochemical response of mice to ADR treatment when fed Mn-sufficient, vitamin E-sufficient (+Mn, +E); Mn-sufficient, low vitamin-E (+Mn, -E); Mn-deficient, vitamin E-sufficient (-Mn, +E); or Mn-deficient, low vitamin-E (-Mn, -E) diets. Mice were injected i.p. with ADR (10 mg/kg bw) or saline (0.9% w/v). ADR injection resulted in a reduction of food intake by 2 days postinjection; by 5 days postinjection ADR-treated mice lost an average of 6.0 g. Heart Mn superoxide dismutase (SOD) activity of -Mn mice was 50% that of +Mn mice; ADR did not affect MnSOD activity. Lipid peroxidation was highest in the -Mn, -E mice, being 2-fold higher than that observed in +Mn, +E mice. ADR injection did not affect lipid peroxidation. An interaction between Fe and ADR treatment was apparent; ADR injected -Mn, -E mice had liver Fe concentrations which were twice that of the saline injected mice fed -Mn, -E diets. These data show that the antioxidant status of an animal may influence ADR toxicity.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004317:Doxorubicin / Q000633:toxicity*; D004347:Drug Interactions; D005260:Female; D006321:Heart / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008054:Lipid Peroxides / Q000378:metabolism*; D008345:Manganese / Q000172:deficiency / Q000494:pharmacology*; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology; D009206:Myocardium / Q000378:metabolism; D013270:Stomach / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D014131:Trace Elements / Q000032:analysis; D014810:Vitamin E / Q000494:pharmacology*
D008054:Lipid Peroxides; D014131:Trace Elements; D014810:Vitamin E; D008345:Manganese; D004317:Doxorubicin; D013482:Superoxide Dismutase