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Doxorubicin-Induced Cardiotoxicity: An Overview on Pre-clinical Therapeutic Approaches

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Abstract

Doxorubicin is an effective chemotherapeutic agent prescribed to treat solid tumors (e.g., ovary, breast, and gastrointestinal cancers). This anti-cancer drug has various side effects, such as allergic reactions, cardiac damage, hair loss, bone marrow suppression, vomiting, and bladder irritation. The most dangerous side effect of doxorubicin is cardiomyopathy, leading to congestive heart failure. The exact mechanisms of doxorubicin-induced cardiotoxicity remain incompletely understood. Alteration in myocardial structure and functional cardiac disorders is provoked by doxorubicin administration; subsequently, cardiomyopathy and congestive heart failure can occur. Congestive heart failure due to doxorubicin is associated with mortality and morbidity. Probably, doxorubicin-induced cardiotoxicity starts from myocardial cell injury and is followed by left ventricular dysfunction. Many factors and multiple pathways are responsible for the creation of doxorubicin-induced cardiotoxicity. Inflammatory cytokines, oxidative stress pathways, mitochondrial damage, intracellular Ca2+ overload, iron-free radical production, DNA, and myocyte membrane injuries have critical roles in the pathophysiology of doxorubicin-induced cardiotoxicity. Unfortunately, there are currently a few medications for the treatment of doxorubicin-induced cardiotoxicity in clinical settings. Extensive basic and clinical researches have been carried out to discover preventive treatments. This review briefly discusses the basic and experimental approaches for treating or preventing doxorubicin-mediated cardiotoxicity based on its pathophysiological mechanisms.

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Funding

This study was supported by Iran National Sciences Foundation (INSF).

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Authors and Affiliations

  1. Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Mohammad Sheibani

  2. Physiology Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Yaser Azizi

  3. Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Yaser Azizi

  4. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran

    Maryam Shayan, Sadaf Nezamoleslami, Faezeh Eslami & Ahmad Reza Dehpour

  5. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Maryam Shayan, Faezeh Eslami & Ahmad Reza Dehpour

  6. Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Mohammad Hadi Farjoo

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  1. Mohammad Sheibani
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  7. Ahmad Reza Dehpour
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Contributions

ARD and MS designed the study. SN, MS, and YA performed the literature search and data analysis. MS and YA drafted the manuscript and edited it. MHF prepared all figures. MS prepared Table 1. FE and SN made critical revision and edited the manuscript. ARD, MS, and MS made final editions to the paper prior to the submission. All authors have read and agreed to the submitted version of the manuscript.

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Correspondence to Ahmad Reza Dehpour.

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The protocol of this study was approved by the Ethics Committee of Tehran University of Medical Sciences.

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Sheibani, M., Azizi, Y., Shayan, M. et al. Doxorubicin-Induced Cardiotoxicity: An Overview on Pre-clinical Therapeutic Approaches. Cardiovasc Toxicol 22, 292–310 (2022). https://doi.org/10.1007/s12012-022-09721-1

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