Document Detail

Physical exercise prior and during treatment reduces sub-chronic doxorubicin-induced mitochondrial toxicity and oxidative stress.
MedLine Citation:
PMID:  25446396     Owner:  NLM     Status:  Publisher    
Doxorubicin (DOX) is an anti-cancer agent whose clinical usage results in a cumulative and dose-dependent cardiotoxicity. We have previously shown that exercise performed prior to DOX treatment reduces the resulting cardiac(mito) toxicity. We sought to determine the effects on cardiac mitochondrial toxicity of two distinct chronic exercise models (endurance treadmill training-TM and voluntary free-wheel activity-FW) when used prior and during DOX treatment. Male-young Sprague-Dawley rats were divided into six groups (n=6 per group): SAL+SED (saline sedentary), SAL+TM (12-weeks TM), SAL+FW (12-weeks FW), DOX+SED (7-weeks of chronic DOX treatment 2mg/kg per week), DOX+TM and DOX+FW. DOX administration started 5weeks after the beginning of the exercise protocol. Heart mitochondrial ultrastructural alterations, mitochondrial function (oxygen consumption and membrane potential), semi-quantification of oxidative phosphorylation (OXPHOS) proteins and their in-gel activity, as well as proteins involved in mitochondrial oxidative stress (SIRT3, p66shc and UCP2), biogenesis (PGC1α and TFAM), acetylation and markers for oxidative damage (carbonyl groups, MDA,SH, aconitase, Mn-SOD activity) were evaluated. DOX treatment resulted in ultrastructural and functional alterations and decreased OXPHOS. Moreover, DOX decreased complex I activity and content, mitochondrial biogenesis (TFAM), increased acetylation and oxidative stress. TM and FW prevented DOX-induced alteration in OXPHOS, the increase in oxidative stress, the decrease in complex V activity and in complex I activity and content. DOX-induced decreases in TFAM and SIRT3 content were prevented by TM only. Both chronic models of physical exercise performed before and during the course of sub-chronic DOX treatment translated into an improved mitochondrial bioenergetic fitness, which may result in part from the prevention of mitochondrial oxidative stress and damage.
Inês Marques-Aleixo; Estela Santos-Alves; Diogo Mariani; David Rizo-Roca; Ana I Padrão; Sílvia Rocha-Rodrigues; Ginés Viscor; J Ramon Torrella; Rita Ferreira; Paulo J Oliveira; José Magalhães; António Ascensão
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-7
Journal Detail:
Title:  Mitochondrion     Volume:  20C     ISSN:  1872-8278     ISO Abbreviation:  Mitochondrion     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-12-3     Completed Date:  -     Revised Date:  2014-12-3    
Medline Journal Info:
Nlm Unique ID:  100968751     Medline TA:  Mitochondrion     Country:  -    
Other Details:
Languages:  ENG     Pagination:  22-33     Citation Subset:  -    
Copyright Information:
Copyright © 2014 © Elsevier B.V. and Mitochondria Research Society. Published by Elsevier B.V. All rights reserved.
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