Doxorubicin: a critical review on toxicity

The anthracycline antibiotic doxorubicin (Adriamycin, DXR) is widely prescribed for the treatment of a variety of human cancers. Unfortunately, its potent antitumor effect is balanced by its toxicity on different organ systems. The most serious long-term side effect of doxorubicin is cardiotoxicity, which can lead to dilated cardiomyopathy (DCM) and congestive heart failure (CHF). Among the different hypothesis, DXR-induced cardiotoxicity has been attributed to increased oxidative stress that leads to damage of macromolecules, membranes and DNA, thereby contributing to cellular damage, energetic deficit and acceleration of cell death through apoptosis and necrosis. Further, membrane lipid per oxidation, mitochondrial damage, iron-dependent oxidative damage to macromolecules, histamine release and disruption of calcium homeostasis are also implicated in the mechanism of drug related side effects. It was supposed that administration of a potent antioxidant and protective drug therapy together with a chemotherapeutic agent may be the proper advance to reduce the toxic side es ffects of drug. This review focuses briefly on DXR-induced side effects and the possible underlying mechanisms of drug related toxicity.