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1 School of Sport and Exercise Science, University of Northern Colorado, Greeley, CO, USA; Rocky Mountain Cancer Rehabilitation Institute, Greeley, CO, USA
* To whom correspondence should be addressed. E-mail: reid.hayward{at}unco.edu.
Doxorubicin (DOX) is a highly effective antineoplastic antibiotic associated with a doselimiting cardiotoxicity that may result in irreversible cardiomyopathy and heart failure. The purpose of this study was to examine the effects of low-intensity exercise training (LIET) during the course of DOX treatment on cardiac function, myosin heavy chain expression, oxidative stress, and apoptosis activation following treatment. Male Sprague-Dawley rats either remained sedentary or were exercise trained on a motorized treadmill at 15 m.min-1, 20 min.d -1, 5 d.wk-1 (M-F) for 2 wks. During the same 2 wk period, DOX (2.5 mg.kg-1) or saline was administered i.p. to sedentary and exercised rats 3 d.wk-1 (MWF) 1-2 hrs following the exercise training sessions (cumulative DOX dose 15 mg.kg-1). Five days following the final injections, hearts were isolated for determination of left ventricular (LV) function, lipid peroxidation, antioxidant enzyme protein expression, heat shock protein-72 (Hsp72) expression, caspase-3 activity, and myosin heavy chain isoform expression. DOX treatment significantly impaired LV function and increased caspase-3 activity in sedentary animals (P < 0.05). LIET attenuated the LV dysfunction and apoptotic signal activation induced by DOX treatment and increased glutathione peroxidase expression, but had no significant effect on lipid peroxidation, protein expression of myosin heavy chain isoforms, Hsp72, or superoxide dismutase isoforms. In conclusion, our data suggest that LIET applied during chronic DOX treatment protects against cardiac dysfunction following treatment, possibly by enhancing antioxidant defenses and inhibiting apoptosis.
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