Vitamin C as a Cardioprotective Agent Against Doxorubicin‐Induced Cardiotoxicity

Doxorubicin is used and highly effective chemotherapeutic agent; however, its clinical utility remains limited by dose‐dependent cardiotoxicity, presenting a significant challenge in cancer management. Growing preclinical research and clinical evidence suggest that the antioxidant vitamin C (ascorbi...

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Main Authors: Hamdi Nsairat, Zainab Lafi, Bassam M. Abualsoud, Belal O. Al‐Najjar, Ali Al‐Samydai, Ghaleb Ali Oriquat, Walhan Alshaer, Abed Alqader Ibrahim, Anthony L. Dellinger
Format: Article
Language:English
Published: Wiley 2025-08-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
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Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.125.042534
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Summary:Doxorubicin is used and highly effective chemotherapeutic agent; however, its clinical utility remains limited by dose‐dependent cardiotoxicity, presenting a significant challenge in cancer management. Growing preclinical research and clinical evidence suggest that the antioxidant vitamin C (ascorbic acid) may confer cardioprotective effects against doxorubicin‐induced cardiotoxicity. In this review, both preclinical and clinical research has been synthesized to assess the potential role of vitamin C in mitigating doxorubicin‐induced cardiotoxicity. Preclinical data have routinely indicated that vitamin C can reduce oxidative stress, preserve mitochondrial function, and modulate proinflammatory cytokine levels. Additionally, animal models have demonstrated promising results in maintaining cardiomyocyte structural integrity. In this capacity, vitamin C may be an effective adjunctive therapeutic for attenuating cardiac injury. Conversely, the clinical data remain variable, with emerging evidence supporting the notion that vitamin C can serve as a safe adjunct that preserves cardiac function during anthracycline therapy. Further investigation is warranted to optimize dosing, timing, and delivery routes and better elucidate the exact molecular mechanisms of these protective effects. This review emphasizes key molecular mechanisms, such as oxidative and nitrosative stress, mitochondrial dysfunction, and inflammatory signaling, in the myocardium, and examines the role of vitamin C supplementation, alone or in combination with doxorubicin, on myocardial damage markers and cardiomyocyte viability.
ISSN:2047-9980