Exercise as a beneficial adjunct therapy during Doxorubicin treatment-Role of mitochondria in cardioprotection

One of the mostly used chemotherapeutic drugs is the highly effective anthracycline Doxorubicin. However, its clinical use is limited by the dose-related and cumulative cardiotoxicity and consequent dysfunction. It has been proposed that the etiology of this toxicity is related to mitochondrial dysfunction. The present review aimed to analyze the promising results regarding the effect of several types of physical exercise in cardiac tolerance of animals treated with acute and sub-chronic doses of Doxorubicin (DOX), highlighting the importance of cardiac mitochondrial-related mechanisms in the process. Physical exercise positively modulates some important cardiac defense systems to antagonize the toxic effects caused by DOX treatment, including antioxidant capacity, the overexpression of heat shock proteins and other anti-apoptotic proteins. An important role in this protective phenotype afforded by exercise should be attributed to mitochondrial plasticity, as related adaptations could be translated into improved cardiac function in the setting of the DOX cardiomyopathy. (C) 2011 Elsevier Ireland Ltd. All rights reserved.