The role of iron in doxorubicin-induced cardiomyopathy

Doxorubicin participates in a wide range of free radical reactions. The drug can undergo one electron reduction to the corresponding semiquinone, leading the generation of superoxide and hydrogen peroxide. Additionally, the drug causes the disappearance of cardiac glutathione peroxidase, leaving the heart with no means of disposing of the hydrogen peroxide thus generated. Doxorubicin also is a powerful iron chelator and the resultant iron-drug complex is an efficient catalyst of the conversion of hydrogen peroxide to the highly reactive hydroxyl radical. Without the drug-iron complex, little or no cardiac production of hydroxyl radical occurs and heart damage does not occur.