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

BACKGROUND AND OBJECTIVE: 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 cardioprotection against DOX-induced cardiotoxicity in the rat. METHODS: Wistar males (weighing 257 ± 28 g) were divided into six 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 and in the 3 and 6 groups received saline solution, DOX 10 mg.kg(-1) and DOX 20 mg.kg(-1), respectively. RESULT: DOX administration (10 and 20 mg.kg(-1)) caused significant increase in MDA and Apelin, an insignificant increase in NO and a significant decrease in SOD, as compared to the C+P group. Three weeks of the pretreatment endurance exercise resulted in a significant increase of Apelin and SOD, an insignificant increase of NO and an insignificant decrease of MDA, as compared to the C+P group. Furthermore, after three weeks of endurance training and DOX treatment with 10mg.kg(-1) and 20mg.kg(-1), a significant increase in apelin and SOD, and a significant decrease in MDA were detected in comparison to C+DOX10 and/or C+DOX20 groups. There was a significant difference between DOX10 mg.kg(-1) and DOX20 mg.kg(-1) treatments in MDA levels only. CONCLUSION: Pretreatment exercise may improve myocardial tolerance to DOX-induced cardiotoxicity by inhibition of oxidative stress and up- regulation of antioxidants in heart tissue.