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Doxorubicin-induced apoptosis: Implications in cardiotoxicity

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Abstract

In this review, we discuss the role of nitric oxide synthase in doxorubicin (DOX)-induced cardiomyopathy, a prominent side effect of DOX chemotherapy in cancer patients. It is becoming increasingly clear that apoptosis of myocardial cells plays a critical role in the onset of cardiomyopathy. DOX exposure to endothelial cells and cardiomyocytes caused apoptotic cell death at sub-micromolar concentrations. DOX-induced generation of H2O2 has been shown to be responsible for this drug's toxicity and apoptosis. H2O2 in turn enhanced endothelial nitric oxide synthase (eNOS) transcription in endothelial cells and myocytes. Antisense eNOS depressed DOX-induced oxidative stress and apoptosis. Redox-metal chelators inhibited DOX-induced apoptosis, clearly suggesting a role for reactive oxygen species in DOX-induced apoptosis. Here, we will focus on the role of eNOS expression, iron chelation, and iron signaling on DOX-mediated apoptosis.

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Kalyanaraman, B., Joseph, J., Kalivendi, S. et al. Doxorubicin-induced apoptosis: Implications in cardiotoxicity. Mol Cell Biochem 234, 119–124 (2002). https://doi.org/10.1023/A:1015976430790

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