Are Oxygen Radicals Responsible for the Acute Cardiotoxicity of Doxorubicin?
Oxygen-derived free radicals nave been implicated as mediators of the acute cardiotoxic effects induced by doxorubicin (DXR) treatment, Superoxide anions (O 2 - ) may be generated by xanthine oxidase or by one-electron reduction of DXR to the corresponding semiquinone and subsequent electron transfer to molecular oxygen. (O 2 - ) generation plays a central role in the sequence of reactions leading to the formation of the more active hydroxyl radical (·OH) according to the Haber-Weiss reaction (figure 1) (1). An additional source of active oxygen species is represented in vivo by the leu Kocytic enzyme myeloperoxidase, since DXR has been shown to stimulate the production of oxidants by neutrophils (2). Free radical-mediated membrane lipo peroxidation and the subsequent impairment of ion transport processes would eventually account for DXR-induced cardiodepressant effects (3–5).
KeywordsXanthine Oxidase Active Oxygen Species Hypochlorous Acid Xanthine Oxidase Inhibition Subsequent Impairment
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