title: Moderate endurance training prevents doxorubicin-induced in vivo mitochondriopathy and reduces the development of cardiac apoptosis.
abstract: The objective of this work was to test the hypothesis that endurance training may be protective against in vivo doxorubicin (DOX)-induced cardiomyopathy through mitochondria-mediated mechanisms. Forty adult (6-8 wk old) male Wistar rats were randomly divided into four groups (n = 10/group): nontrained, nontrained + DOX treatment (20 mg/kg), trained (14 wk of endurance treadmill running, 60-90 min/day), and trained + DOX treatment. Mitochondrial respiration, calcium tolerance, oxidative damage, heat shock proteins (HSPs), antioxidant enzyme activity, and apoptosis markers were evaluated. DOX induces mitochondrial respiratory dysfunction, oxidative damage, and histopathological lesions and triggers apoptosis (P < 0.05, n = 10). However, training limited the decrease in state 3 respiration, respiratory control ratio (RCR), uncoupled respiration, aconitase activity, and protein sulfhydryl content caused by DOX treatment and prevented the increased sensitivity to calcium in nontrained + DOX-treated rats (P < 0.05, n = 10). Moreover, training inhibited the DOX-induced increase in mitochondrial protein carbonyl groups, malondialdehyde, Bax, Bax-to-Bcl-2 ratio, and tissue caspase-3 activity (P < 0.05, n = 10). Training also increased by approximately 2-fold the expression of mitochondrial HSP-60 and tissue HSP-70 (P < 0.05, n = 10) and by approximately 1.5-fold the activity of mitochondrial and cytosolic forms of SOD (P < 0.05, n = 10). We conclude that endurance training protects heart mitochondrial respiratory function from the toxic effects of DOX, probably by improving mitochondrial and cell defense systems and reducing cell oxidative stress. In addition, endurance training limited the DOX-triggered apoptosis.
authors.affiliation: Department of Sport Biology, Faculty of Sport Sciences, Univ. of Porto, Rua Dr. Plácido Costa, 91, 4200-450 Porto, Portugal. aascensao@fcdef.up.pt
authors.forename: António
authors.initials: A
authors.lastname: Ascensão
authors.forename: José
authors.initials: J
authors.lastname: Magalhães
authors.forename: José M C
authors.initials: JM
authors.lastname: Soares
authors.forename: Rita
authors.initials: R
authors.lastname: Ferreira
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Neuparth
authors.forename: Franklim
authors.initials: F
authors.lastname: Marques
authors.forename: Paulo J
authors.initials: PJ
authors.lastname: Oliveira
authors.forename: José A
authors.initials: JA
authors.lastname: Duarte
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000517:prevention & control*; D004317:Doxorubicin / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000502:physiology; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D028361:Mitochondrial Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D018384:Oxidative Stress; D010101:Oxygen Consumption / Q000187:drug effects; D010805:Physical Conditioning, Animal; D010807:Physical Endurance; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004317:Doxorubicin