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

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.