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Influence of dietary manganese and vitamin E on adriamycin toxicity in mice
Abstract:
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.
Insights
Adriamycin toxicity in mice was influenced by antioxidant status. Dietary manganese and vitamin E levels affected lipid peroxidation and iron levels, indicating their role in mitigating drug-induced damage.
Area of Science:
- Biochemistry
- Toxicology
- Nutritional Science
Background:
- Adriamycin (ADR) is known to cause cardiac toxicity.
- Increased lipid peroxidation is a proposed mechanism for ADR-induced damage.
- The role of antioxidant status in modulating ADR toxicity requires further investigation.
Purpose of the Study:
- To evaluate the biochemical response of mice to Adriamycin (ADR) treatment.
- To assess the impact of dietary manganese (Mn) and vitamin E (E) sufficiency on ADR-induced toxicity.
- To investigate the relationship between antioxidant status and ADR cardiotoxicity.
Main Methods:
- Mice were fed diets varying in manganese and vitamin E content (+Mn/+E, +Mn/-E, -Mn/+E, -Mn/-E).
- Mice were injected intraperitoneally with Adriamycin (ADR) or saline.
- Measurements included food intake, body weight, heart Mn superoxide dismutase (MnSOD) activity, lipid peroxidation, and liver iron (Fe) concentration.
Main Results:
- ADR administration reduced food intake and caused weight loss in mice.
- Manganese deficiency significantly reduced heart MnSOD activity.
- Lipid peroxidation was highest in mice fed a diet deficient in both manganese and vitamin E (-Mn/-E), and ADR did not directly affect lipid peroxidation levels. Liver iron concentrations were elevated in ADR-injected -Mn/-E mice compared to controls.
Conclusions:
- Dietary antioxidant status, particularly manganese and vitamin E, influences biochemical responses to Adriamycin.
- Manganese deficiency exacerbates lipid peroxidation and alters iron metabolism in the context of ADR treatment.
- These findings suggest that the antioxidant status of an animal plays a significant role in modulating Adriamycin toxicity.