Cardiotoxicity of doxorubicin: Causes, diagnosis, consequences and possibilities of prevention

Abstract

Introduction: Doxorubicin is an antibiotic from the anthracycline group, with clinical use limited by adverse reactions, primarily cardiotoxicity. Material and Methods: This article provides an overview of therapeutic and toxic doses of doxorubicin, the mechanism of side effects, markers for early detection as well as currently available preparations for preventing its toxicity. We searched PubMed, Google Scholar, SCIndex, Dimension, Scopus and Google for English and Serbian language abstracts, using the searching terms "doxorubicin", "cardiotoxicty", "carotenoids", "oncology", "oxidative stress", "DNA damage" and "biomarkers". Topic: The mechanism of side effects is still unclear and is considered to be multifactorial including ROS overproduction, reducing levels of endogenous antioxidants, DNA damage, large drug accumulation in cardiac tissue, calcium overload, histamine release, and impairment of autoimmune regulation of cardiac function Manifestations of cardiotoxicity are mainly acute (appear inside 24h atypical changes of ST segment, decrease in QRS complex voltage, tachycardia and supraventricular extrasystoles are observed, but can also be subacute and chronic (cardiomyocyte edema, disorganzation, fibroblast proliferation, necrosis). Diagnosis of cardiotoxicity is based on ECG, ECHO, and biochemical markers, among which the most important are troponins, while pathohistological verification is necessary for the final diagnosis. Some medications (carvedilol, atorvastatin) have showed some level of cardioprotection against DOX, but there is no overall agreement on their administration solely for this purpose. An increasing number of studies have tested various dietary supplements and natural preparations (already in the human diet) in order to discover those that could completely prevent or reduce the toxic effects of doxorubicin, with special focus on carotenoids. Conclusion: Cardiotoxicity is the leading side effect of doxorubicin, and therefore there is an active search for either new biomarkers and/or diagnostic protocols that would detect toxicity in time, as well as substances able to prevent the occurrence or alleviate DOXinduced cardiotoxicity.