Cardioprotective effects of aerobic regular exercise against doxorubicin- induced oxidative stress in rat

Doxorubicin (DOX) is an anthracycline antibiotic that is widely used as an anticancer agent. However, the clinical use of DOX is limited due to its cardiotoxic side effects. Few studies have assessed pretreatment effects of chronically exercise against doxorubicin-induced cardiotoxicity. The aim of this study was to determine cardioprotective effects of aerobic regular exercise against doxorubicin-induced oxidative stress in rat. Forty-eight Wistar male rats were randomly assigned to sedentary and trained groups. Training program included treadmill running between 25 to 54 min/day and 15 to 20 m/min, 5 days/week for 6 weeks. The biomarkers related to oxidative stress were assessed in heart tissue after administration of the saline solution (0.9% NaCl i.p) and/or DOX 20 mg/kg and DOX 10 mg/kg. Doxorubicin administration (10 and 20 mg.kg-1) causes an imbalance in the oxidant/antioxidant markers in heart. Six weeks of the aerobic training led to a significant increase of apelin, nitric oxide(NO), superoxide dismutase(SOD) and an insignificant decrease of malondialdehyde(MDA), as compared to sedentary+placebo group. However, after six weeks of aerobic training and DOX treatment with 10 and 20 mg.kg-1, a significant increase in apelin and SOD, and a significant decrease in MDA were detected in comparison to sedentary+DOX 10 and/ or sedentary+DOX 20 groups. However, there was a significant difference between DOX 10 mg.kg-1 and DOX 20 mg.kg-1 treatments in NO and SOD levels, only. Our study suggests that cardioprotection induced by chronically exercise in DOX treated rats was associated with inhibition of oxidative stress and the up-regulation of antioxidant enzymes.   Key words: Cardiotoxicity, doxorubicin, antioxidant, endurance training, rat.