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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author 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
author_facet 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
author_sort Hamdi Nsairat
collection DOAJ
description 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.
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series Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
spelling doaj-art-09e61a8fda4e422b90c9ed5a1bc2de6f2025-08-20T07:24:49ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802025-08-01141610.1161/JAHA.125.042534Vitamin C as a Cardioprotective Agent Against Doxorubicin‐Induced CardiotoxicityHamdi Nsairat0Zainab Lafi1Bassam M. Abualsoud2Belal O. Al‐Najjar3Ali Al‐Samydai4Ghaleb Ali Oriquat5Walhan Alshaer6Abed Alqader Ibrahim7Anthony L. Dellinger8Pharmacological and Diagnostic Research Center, Faculty of Pharmacy Al‐Ahliyya Amman University Amman JordanPharmacological and Diagnostic Research Center, Faculty of Pharmacy Al‐Ahliyya Amman University Amman JordanPharmacological and Diagnostic Research Center, Faculty of Pharmacy Al‐Ahliyya Amman University Amman JordanPharmacological and Diagnostic Research Center, Faculty of Pharmacy Al‐Ahliyya Amman University Amman JordanPharmacological and Diagnostic Research Center, Faculty of Pharmacy Al‐Ahliyya Amman University Amman JordanPharmacological and Diagnostic Research Center, Faculty of Allied Medical Sciences Al‐Ahliyya Amman University Amman JordanCell Therapy Center The University of Jordan Amman JordanDepartment of Nanoscience, Joint School of Nanoscience and Nanoengineering University of North Carolina at Greensboro Greensboro NC USADepartment of Nanoscience, Joint School of Nanoscience and Nanoengineering University of North Carolina at Greensboro Greensboro NC USADoxorubicin 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.https://www.ahajournals.org/doi/10.1161/JAHA.125.042534cardioprotectiondoxorubicin‐induced cardiotoxicityoxidative stressreactive oxygen speciesvitamin C
spellingShingle 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
Vitamin C as a Cardioprotective Agent Against Doxorubicin‐Induced Cardiotoxicity
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
cardioprotection
doxorubicin‐induced cardiotoxicity
oxidative stress
reactive oxygen species
vitamin C
title Vitamin C as a Cardioprotective Agent Against Doxorubicin‐Induced Cardiotoxicity
title_full Vitamin C as a Cardioprotective Agent Against Doxorubicin‐Induced Cardiotoxicity
title_fullStr Vitamin C as a Cardioprotective Agent Against Doxorubicin‐Induced Cardiotoxicity
title_full_unstemmed Vitamin C as a Cardioprotective Agent Against Doxorubicin‐Induced Cardiotoxicity
title_short Vitamin C as a Cardioprotective Agent Against Doxorubicin‐Induced Cardiotoxicity
title_sort vitamin c as a cardioprotective agent against doxorubicin induced cardiotoxicity
topic cardioprotection
doxorubicin‐induced cardiotoxicity
oxidative stress
reactive oxygen species
vitamin C
url https://www.ahajournals.org/doi/10.1161/JAHA.125.042534
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