Document Detail


Voluntary exercise protects against acute doxorubicin cardiotoxicity in the isolated perfused rat heart.
MedLine Citation:
PMID:  15845878     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The clinical use of doxorubicin (DOX) is limited by a dose-dependent cardiotoxicity. The purpose of this study was to determine whether voluntary exercise training would confer protection against DOX cardiotoxicity in the isolated perfused rat heart. Female Sprague-Dawley rats were randomly assigned to standard holding cages or cages with running wheels for 8 wk. Twenty-four hours after the sedentary (SED) or voluntary exercise (VEX) running period, rats were anesthetized with pentobarbital sodium, and hearts were isolated and perfused with oxygenated Krebs-Henseleit (KH) buffer at a constant flow of 15 ml/min. After a 20-min stabilization period, hearts were paced at 300 beats per minute and perfused with KH buffer containing 10 microM DOX for 60 min. A set of control hearts from SED and VEX rats were perfused under identical conditions without DOX for the same period. DOX perfusion led to significant decreases in left ventricular developed pressure, +dP/dt, and -dP/dt, and significant increases in LV lipid peroxidation in sedentary rats compared with non-DOX controls (P < 0.05). Prior voluntary exercise training attenuated these DOX-induced effects and was associated with a significant increase (78%, P < 0.05) in heat shock protein (HSP72), but not mitochondrial isoform of SOD (MnSOD) or CuZnSOD protein expression in the hearts of wheel-run animals. These data indicate that chronic physical activity may provide resistance against the cardiac dysfunction and oxidative damage associated with DOX exposure and provide novel evidence of HSP72 induction in the heart after voluntary exercise.
Authors:
Adam J Chicco; Carole M Schneider; Reid Hayward
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-04-21
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  289     ISSN:  0363-6119     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2005 Aug 
Date Detail:
Created Date:  2005-07-14     Completed Date:  2005-09-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R424-R431     Citation Subset:  IM    
Affiliation:
School of Sport and Exercise Science, University of Northern Colorado, Greeley, CO 80639, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibiotics, Antineoplastic / poisoning*
Doxorubicin / poisoning*
Female
HSP72 Heat-Shock Proteins
Heart / drug effects*,  physiology*
Heart Ventricles
Heat-Shock Proteins / metabolism
Lipid Peroxidation / drug effects
Motor Activity / physiology*
Myocardium / metabolism
Perfusion
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; 0/Heat-Shock Proteins; 23214-92-8/Doxorubicin; EC 1.15.1.1/Superoxide Dismutase

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