Low-intensity exercise training during doxorubicin treatment protects against cardiotoxicity

• Published in: Journal of applied physiology (1985) 2006-02, Vol.100 (2), p.519-527
• Main Authors: Chicco, Adam J, Hydock, David S, Schneider, Carole M, Hayward, Reid
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - adverse effects; Apoptosis; Biological and medical sciences; Caspase 3 - metabolism; Doxorubicin - administration & dosage; Doxorubicin - adverse effects; Exercise; Fundamental and applied biological sciences. Psychology; Glutathione Peroxidase - metabolism; Heart; Heart - drug effects; Heart failure; Heart Ventricles - enzymology; Heart Ventricles - pathology; Male; Myocardium - enzymology; Myocardium - pathology; Physical Conditioning, Animal; Rats; Rats, Sprague-Dawley; Ventricular Dysfunction, Left - enzymology; Ventricular Dysfunction, Left - etiology; Ventricular Dysfunction, Left - prevention & control
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00148.2005

School of Sport and Exercise Science and the Rocky Mountain Cancer Rehabilitation Institute, University of Northern Colorado, Greeley, Colorado Submitted 4 February 2005 ; accepted in final form 1 October 2005 Doxorubicin (Dox) is a highly effective antineoplastic antibiotic associated with a dose-limiting 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, 20 min/day, 5 days/wk (Monday through Friday) for 2 wk. During the same 2-wk period, Dox (2.5 mg/kg) or saline was administered intraperitoneally to sedentary and exercised rats 3 days/wk (Monday, Wednesday, Friday) 1–2 h following the exercise training sessions (cumulative Dox dose: 15 mg/kg). Five days following the final injections, hearts were isolated for determination of left ventricular (LV) function, lipid peroxidation, antioxidant enzyme protein expression, 72-kDa heat shock protein 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 it had no significant effect on lipid peroxidation, protein expression of myosin heavy chain isoforms, 72-kDa heat shock protein, 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. adriamycin; apoptosis; physical activity; cardioprotection; myosin heavy chain Address for reprint requests and other correspondence: R. Hayward, Sport and Exercise Science, Univ. of Northern Colorado, Greeley, CO 80639 (e-mail: reid.hayward{at}unco.edu )