Related Experiment Videos
Effects by doxorubicin on the myocardium are mediated by oxygen free radicals
1Department of Pathology and Laboratory Medicine, University of Cincinnati, OH 45267-0529, USA.
Abstract:
We hypothesized that doxorubicin (DOX) induces cardiotoxicity of myocardium via oxygen radicals. The present study is aimed at examining the membrane alterations by oxygen radicals generated by DOX in adult rats and cultured neonatal myocytes. Our results showed that DOX 1) decreased beta-adrenoceptor (BAR) density in the cell membrane, 2) increased the membrane permeability of cultured neonatal rat myocytes and 3) altered the ultrastructure of myofibrils and subplasmalemmal actin networks. These effects were reproducible by exogenous hydrogen peroxide. The antioxidant melatonin (MLT) inhibited enzyme leakage and peroxidation in a concentration-dependent manner. It is concluded that DOX induces cardiotoxicity through lipid peroxidation and melatonin is an effective antioxidant against the reactive oxygen intermediates generated by DOX.
Insights
Doxorubicin (DOX) causes heart damage by generating oxygen radicals, affecting cell membranes and structures. The antioxidant melatonin (MLT) effectively protects against this cardiotoxicity.
Area of Science:
- Cardiology
- Toxicology
- Cell Biology
Background:
- Doxorubicin (DOX) is a widely used chemotherapy agent with known cardiotoxicity.
- The precise mechanisms underlying DOX-induced cardiotoxicity, particularly concerning membrane alterations, require further elucidation.
- Oxygen radicals are implicated in various forms of cellular damage, including cardiac tissue injury.
Purpose of the Study:
- To investigate the role of oxygen radicals in doxorubicin-induced cardiotoxicity.
- To examine the specific membrane alterations caused by DOX in cardiac cells.
- To evaluate the protective effects of the antioxidant melatonin (MLT) against DOX-induced damage.
Main Methods:
- Experiments were conducted using adult rats and cultured neonatal rat myocytes.
- Doxorubicin (DOX) was administered to induce cardiotoxicity.
- Measurements included beta-adrenoceptor (BAR) density, cell membrane permeability, and ultrastructural analysis.
- Exogenous hydrogen peroxide was used to mimic DOX-induced effects.
- The antioxidant melatonin (MLT) was tested for its protective capabilities.
Main Results:
- DOX significantly decreased beta-adrenoceptor (BAR) density in cardiac cell membranes.
- DOX increased the membrane permeability of cultured neonatal rat myocytes.
- Ultrastructural changes were observed in myofibrils and subplasmalemmal actin networks following DOX treatment.
- These DOX-induced effects were reproducible by exogenous hydrogen peroxide.
- Melatonin (MLT) demonstrated a concentration-dependent inhibition of enzyme leakage and lipid peroxidation.
Conclusions:
- Doxorubicin (DOX) induces cardiotoxicity primarily through the generation of oxygen radicals and subsequent lipid peroxidation.
- DOX-induced membrane alterations include decreased BAR density and increased permeability.
- Melatonin (MLT) is an effective antioxidant, mitigating DOX-induced cardiotoxicity by scavenging reactive oxygen intermediates.