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Ascorbic acid and adriamycin toxicity
K Shimpo1, T Nagatsu, K Yamada
1Institute for Comprehensive Medical Science, School of Medicine, Fujita Health University, Aichi, Japan.
Abstract:
Adriamycin (ADR) is effective against a wide range of human neoplasms. However, its clinical use is compromised by serious cardiac toxicity, possibly through induction of peroxidation in cardiac lipids. Ascorbic acid, a potent antioxidant, was examined for effect in reducing ADR toxicity in mice and guinea pigs. Ascorbic acid had no effect on the antitumor activity of ADR in mice inoculated with leukemia L1210 or Ehrlich ascites carcinoma, but it significantly prolonged the life of animals treated with ADR. ADR elevated lipid peroxide levels in mouse heart, and ascorbic acid prevented the elevation. The significant prevention of ADR-induced cardiomyopathy in guinea pigs by ascorbic acid was proved by electron microscopy. Ascorbic acid and the derivatives may delay general toxicity of ADR and also prevent the cardiac toxicity. The results also suggest the clinical efficacy of the combined treatment of ADR and ascorbic acid or the derivatives.
Insights
Adriamycin (ADR) chemotherapy can cause heart damage. Ascorbic acid, an antioxidant, did not affect ADR
Area of Science:
- Oncology
- Cardiology
- Pharmacology
Background:
- Adriamycin (ADR) is a potent chemotherapy drug effective against various human neoplasms.
- A significant limitation of ADR therapy is its cardiotoxicity, potentially mediated by lipid peroxidation in cardiac tissues.
- Ascorbic acid is a well-known antioxidant with potential to mitigate oxidative stress.
Purpose of the Study:
- To investigate the efficacy of ascorbic acid in reducing Adriamycin-induced toxicity, particularly cardiotoxicity.
- To evaluate the impact of ascorbic acid on the antitumor activity and overall survival in ADR-treated animals.
- To assess the protective effects of ascorbic acid against ADR-induced cardiac damage at a cellular level.
Main Methods:
- Animal models (mice and guinea pigs) were used to assess ADR toxicity and the effects of ascorbic acid.
- Antitumor activity was evaluated in mice bearing leukemia L1210 or Ehrlich ascites carcinoma.
- Lipid peroxide levels in cardiac tissue and ultrastructural changes in the heart were analyzed.
- Survival rates of animals treated with ADR alone versus ADR combined with ascorbic acid were compared.
Main Results:
- Ascorbic acid did not compromise the antitumor efficacy of ADR against tested neoplasms.
- Ascorbic acid significantly prolonged the survival of animals treated with ADR.
- ADR treatment increased lipid peroxide levels in mouse hearts, an effect prevented by ascorbic acid.
- Electron microscopy confirmed that ascorbic acid significantly prevented ADR-induced cardiomyopathy in guinea pigs.
Conclusions:
- Ascorbic acid demonstrates a protective effect against Adriamycin-induced cardiotoxicity without diminishing its anticancer activity.
- Ascorbic acid and its derivatives show potential for mitigating both general and cardiac toxicity associated with ADR therapy.
- Combined treatment with ADR and ascorbic acid or its derivatives may offer a safer and more effective therapeutic strategy for cancer patients.