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Doxorubicin-induced apoptosis: implications in cardiotoxicity
B Kalyanaraman1, Joy Joseph, Shashi Kalivendi
1Biophysics Research Institute and Free Radical Research Center, Medical College of Wisconsin, Milwaukee 53226, USA. balarama@mcw.edu
Molecular and Cellular Biochemistry
|August 7, 2002
Summary
Doxorubicin (DOX) chemotherapy can cause heart damage through apoptosis. This review explores how nitric oxide synthase (NOS) and reactive oxygen species contribute to DOX-induced cardiomyopathy, suggesting potential therapeutic targets.
Area of Science:
- Cardiology
- Oncology
- Biochemistry
Background:
- Doxorubicin (DOX) chemotherapy is vital for cancer treatment but causes cardiotoxicity, a major side effect.
- Myocardial cell apoptosis is a key mechanism in the development of DOX-induced cardiomyopathy.
- DOX exposure induces cell death in endothelial cells and cardiomyocytes, mediated by reactive oxygen species like hydrogen peroxide (H2O2).
Purpose of the Study:
- To review the role of nitric oxide synthase (NOS) in doxorubicin (DOX)-induced cardiomyopathy.
- To elucidate the mechanisms linking DOX toxicity, oxidative stress, and apoptosis.
- To focus on the influence of eNOS expression, iron chelation, and iron signaling in DOX-mediated apoptosis.
Main Methods:
- Review of existing literature on DOX cardiotoxicity, apoptosis, and the role of nitric oxide synthase.
- Analysis of studies investigating the effects of DOX on endothelial cells and cardiomyocytes.
- Examination of research on reactive oxygen species, H2O2, and their interaction with eNOS.
Main Results:
- DOX induces apoptotic cell death in cardiac and endothelial cells.
- Hydrogen peroxide (H2O2) generated by DOX enhances endothelial nitric oxide synthase (eNOS) transcription.
- Inhibition of eNOS and the use of redox-metal chelators reduce DOX-induced oxidative stress and apoptosis.
Conclusions:
- Nitric oxide synthase, particularly eNOS, plays a significant role in DOX-induced cardiotoxicity.
- Reactive oxygen species and iron signaling are critical mediators of DOX-induced apoptosis.
- Targeting eNOS expression and iron chelation may offer protective strategies against DOX cardiotoxicity.