Endurance exercise training attenuates morphological signs of cardiac muscle damage induced by doxorubicin in male mice

The purpose of this study was to determine the effect of endurance swimming training (14 wks, 5day/wk, 1h/day) on cardiac muscle tolerance to in vivo doxorubicin (DOX)-induced toxicity, analysing quantitative and qualitative histological signs of muscle damage and plasma cardiac troponin I (cTnI). Thirty-two Charles River CD1 male mice were randomly assigned to non-trained placebo (NT+P, n=8), non-trained DOX (NT+DOX, n=8), trained placebo (T+P, n=8) and trained DOX (T+DOX, n=8). DOX was administered i.p. 24 hours after the last exercise bout, in a single dose of 20mg.kg -1 . Twenty-four hours after DOX treatment, the animals were sacrificed and aliquots of plasma were obtained for measuring plasma concentrations of cTnI; cardiac ventricles were extracted for semi quantitative and qualitative morphological analysis of tissue damage using light and electron microscopy. DOX treatment per se elevated (p<0.05) the levels of cTnI, which were significantly attenuated in T+DOX group. Morphological examination revealed that the elevated extension and severity damage scores in sedentary DOX hearts were significantly (p<0.05) reduced in trained group treated with DOX. Moreover, the percentage the total abnormal mitochondria exhibiting extensive loss of cristae, intramitochondrial vacuoles and notorious myelin figures were 0%, 88.3%, 2.9% and 10.1% for NT+P, NT+DOX, T+P and T+DOX, respectively. According to our data, endurance training seems to attenuate the severe morphological and biochemical signs of cardiac muscle injury induced by DOX treatment. These improvements in trained hearts were accompanied by an enhanced mitochondrial protection against DOX side effects.