Doxorubicin-induced cardiomyopathy: an update beyond oxidative stress and myocardial cell death

The clinical use of doxorubicin is limited by the total cumulative dose due to its dose-related cardiac toxicities. Clinical manifestation of doxorubicin-mediated cardiotoxicity may be presented in forms of arrhythmia, cardiomyopathy, or congestive heart failure. Cardiomyopathy is a condition in which the cardiac muscles are damaged, leading to cardiac dysfunctions. Mechanistically, the damage of cardiomyocytes is believed to be mediated primarily by oxidative stress. Cardiac mitochondrial damage is evident within a few hours following exposure to doxorubicin. When cardiomyocytes are chronically exposed to doxorubicin, the damages are even more pronounced. In animal models of doxorubicin-induced cardiotoxicity, lacking multidrug-resistance associated protein 1 intensifies damage of the cardiac nuclei and causes more severe left ventricular dysfunction. It appears that cardiac tissue damage induced by doxorubicin is not confined to cardiomyocytes; endothelial cells are affected by doxorubicin as well. Current evidence has indicated that there is a cross-talk between endothelial cells and cardiomyocytes. The purpose of this article is to briefly review and update the current findings associated with doxorubicin-induced cardiomyopathy.