Hydroxytyrosol ameliorates oxidative stress and mitochondrial dysfunction in doxorubicin-induced cardiotoxicity in rats with breast cancer.

Abstract

Oxidative stress is involved in several processes including cancer, aging and cardiovascular disease, and has been shown to potentiate the therapeutic effect of drugs such as doxorubicin. Doxorubicin causes significant cardiotoxicity characterized by marked increases in oxidative stress and mitochondrial dysfunction. Herein, we investigate whether doxorubicin-associated chronic cardiac toxicity can be ameliorated with the antioxidant hydroxytyrosol in rats with breast cancer. Thirty-six rats bearing breast tumors induced chemically were divided into 4 groups: control, hydroxytyrosol (0.5mg/kg, 5days/week), doxorubicin (1mg/kg/week), and doxorubicin plus hydroxytyrosol. Cardiac disturbances at the cellular and mitochondrial level, mitochondrial electron transport chain complexes I-IV and apoptosis-inducing factor, and oxidative stress markers have been analyzed. Hydroxytyrosol improved the cardiac disturbances enhanced by doxorubicin by significantly reducing the percentage of altered mitochondria and oxidative damage. These results suggest that hydroxytyrosol improve the mitochondrial electron transport chain. This study demonstrates that hydroxytyrosol protect rat heart damage provoked by doxorubicin decreasing oxidative damage and mitochondrial alterations.

• Authors: Sergio Granados-Principal, Nuri El-Azem, Reinald Pamplona, Cesar Ramirez-Tortosa, Mario Pulido-Moran, Laura Vera-Ramirez, Jose L Quiles, Pedro Sanchez-Rovira, Alba Naudí, Manuel Portero-Otin, Patricia Perez-Lopez, Mcarmen Ramirez-Tortosa
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 90 Issue 1 Pg. 25-33 (Jul 01 2014) ISSN: 1873-2968 [Electronic] England
• PMID: 24727461 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Antioxidants
• Apoptosis Inducing Factor
• Fatty Acids
• 3,4-dihydroxyphenylethanol
• Doxorubicin
• Electron Transport Complex II
• Electron Transport Complex IV
• Electron Transport Complex I
• Electron Transport Complex III
• Phenylethyl Alcohol

Topics

• Animals
• Antioxidants (pharmacology)
• Apoptosis Inducing Factor (metabolism)
• Doxorubicin
• Electron Transport Complex I (metabolism)
• Electron Transport Complex II (metabolism)
• Electron Transport Complex III (metabolism)
• Electron Transport Complex IV (metabolism)
• Fatty Acids (chemistry, metabolism)
• Female
• Gas Chromatography-Mass Spectrometry
• Heart Diseases (chemically induced, complications, metabolism)
• Immunoblotting
• Mammary Neoplasms, Animal (complications, metabolism)
• Microscopy, Electron
• Mitochondria, Heart (drug effects, metabolism, ultrastructure)
• Oxidation-Reduction (drug effects)
• Oxidative Stress (drug effects)
• Phenylethyl Alcohol (analogs & derivatives, pharmacology)
• Rats
• Rats, Sprague-Dawley