Low-intensity exercise training during doxorubicin treatment protects against cardiotoxicity
- 1 February 2006
- journal article
- Published by American Physiological Society in Journal of Applied Physiology
- Vol. 100 (2), 519-527
- https://doi.org/10.1152/japplphysiol.00148.2005
Abstract
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.Keywords
This publication has 28 references indexed in Scilit:
- Moderate endurance training prevents doxorubicin-induced in vivo mitochondriopathy and reduces the development of cardiac apoptosisAmerican Journal of Physiology-Heart and Circulatory Physiology, 2005
- Voluntary exercise protects against acute doxorubicin cardiotoxicity in the isolated perfused rat heartAmerican Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2005
- Endurance training attenuates doxorubicin-induced cardiac oxidative damage in miceInternational Journal of Cardiology, 2005
- Loss of exercise-induced cardioprotection after cessation of exerciseJournal of Applied Physiology, 2004
- Exercise, heat shock proteins, and myocardial protection from I-R injuryMedicine & Science in Sports & Exercise, 2001
- Effect of Doxorubicin on Postrest Contraction in Isolated Rat HeartsJournal of Cardiovascular Pharmacology, 1995
- Role of cytosolic Ca2+ and protein kinases in the induction of the hsp70 geneKidney International, 1994
- Induction of stress proteins in cultured myogenic cells. Molecular signals for the activation of heat shock transcription factor during ischemia.JCI Insight, 1992
- HSP70 and other possible heat shock or oxidative stress proteins are induced in skeletal muscle, heart, and liver during exerciseFree Radical Biology & Medicine, 1991
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976