Document Detail


Exercise training attenuates acute doxorubicin-induced cardiac dysfunction.
MedLine Citation:
PMID:  16495754     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The use of doxorubicin, a highly effective antitumor antibiotic, is limited by a dose-dependent cardiotoxicity. The purpose of this study was to determine whether chronic exercise training (ET) prior to doxorubicin treatment would preserve cardiac function and reduce myocardial oxidative stress following treatment. Rats were exercise trained on a motorized treadmill or confined to sedentary cage activity for 12 weeks, then administered an intraperitoneal injection of doxorubicin (15 mg/kg) or 0.9% saline. Five days following the injections, hearts were isolated and Langendorf perfused to assess cardiac function and then processed for biochemical analyses. Doxorubicin treatment induced significant inotropic, lusitropic, and chronotropic cardiac dysfunction, reduced coronary flow, and increased cardiac lipid peroxidation in the sedentary animals. Doxorubicin treatment was also associated with a decrease in cardiac manganese superoxide dismutase protein expression and an increase in heat shock protein-72 (Hsp72) compared with saline-treated animals. Exercise training attenuated doxorubicin-induced cardiac dysfunction, and lipid peroxidation, and led to a greater cardiac expression of Hsp72 compared with the sedentary animals. The results of this study demonstrate for the first time that chronic exercise training before doxorubicin treatment protects against cardiac dysfunction following treatment, and provide evidence for a sustained increase in myocardial Hsp72 following exercise training and doxorubicin treatment in vivo.
Authors:
Adam J Chicco; Carole M Schneider; Reid Hayward
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Publication Detail:
Type:  Comparative Study; In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  47     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-02-23     Completed Date:  2006-07-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  182-9     Citation Subset:  IM    
Affiliation:
School of Sport and Exercise Science and the Rocky Mountain Cancer Rehabilitation Institute University of Northern Colorado, Greeley, Colorado 80639, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibiotics, Antineoplastic / toxicity*
Doxorubicin / toxicity*
HSP72 Heat-Shock Proteins / metabolism
Heart / drug effects*,  physiology*
Heart Diseases / chemically induced
Heart Ventricles
Lipid Peroxidation / drug effects
Male
Myocardium / metabolism
Perfusion
Physical Conditioning, Animal / physiology*
Random Allocation
Rats
Rats, Sprague-Dawley
Superoxide Dismutase / metabolism
Time Factors
Ventricular Function, Left / drug effects
Chemical
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/HSP72 Heat-Shock Proteins; 23214-92-8/Doxorubicin; EC 1.15.1.1/Superoxide Dismutase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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