Is Short-term Exercise a Therapeutic Tool for Improvementof Cardioprotection Against DOX-induced Cardiotoxicity? An Experimental Controlled Protocol in Rats

Abstract

Background and <br/><b>Objective</b>: Cardiotoxicity and oxidative stress is a life-threatening side effect of doxorubicin(DOX). We investigate the effects of short-term exercise as therapeutic tool for improvement of cardioprotectionagainst DOX-induced cardiotoxicity in the rat. <br/><b>Methods</b>: Wistar males (weighing 257±28 g) were divided intosix groups: (1) control+placebo (2) control+DOX 10 mg.kg-1 (3) control+DOX 20mg.kg-1 (4) training+placebo (5)training+ DOX10 mg.kg-1 (6) training+DOX 20mg.kg-1. Cardiotoxicity was induced by DOX (10 and 20 mg.kg-1).The rats in groups 4, 5 and 6 experienced treadmill running of 25 to 39 min.day-1 and 15 to 17 m.min-1, 5 days/wk for 3 wk. At the end of the endurance training program, rats in the 1 and 4 groups, in the 2 and 5 groups andin the 3 and 6 groups received saline solution, DOX 10 mg.kg-1 and DOX 20 mg.kg-1, respectively. <br/><b>Result</b>: DOXadministration (10 and 20 mg.kg-1) caused significant increase in MDA and Apelin, an insignificant increase in NOand a significant decrease in SOD, as compared to the C+P group. Three weeks of the pretreatment enduranceexercise resulted in a significant increase of Apelin and SOD, an insignificant increase of NO and an insignificantdecrease of MDA, as compared to the C+P group. Furthermore, after three weeks of endurance training and DOXtreatment with 10mg.kg-1 and 20mg.kg-1, a significant increase in apelin and SOD, and a significant decrease inMDA were detected in comparison to C+DOX10 and/or C+DOX20 groups. There was a significant differencebetween DOX10 mg.kg-1 and DOX20 mg.kg-1 treatments in MDA levels only. <br/><b>Conclusion</b>: Pretreatment exercisemay improve myocardial tolerance to DOX-induced cardiotoxicity by inhibition of oxidative stress and upregulationof antioxidants in heart tissue.