Moderate endurance training prevents doxorubicin-induced in vivo mitochondriopathy and reduces the development of cardiac apoptosis

• Type: Article in International Scientific Journal
• Date: 2005

Authors

Ascensao, A (Author) FADEUP; Magalhaes, J (Author) FADEUP; Soares, JMC (Author) Other; Ferreira, R (Author) Other; Neuparth, MJ (Author) Other; Marques, F (Author) FFUP; Oliveira, PJ (Author) Other; Duarte, JA (Author) FADEUP

Journal

Title: American Journal of Physiology - Heart and Circulatory Physiology

Vol. 289

Pages: H722-H731

ISSN: 0363-6135

Publisher: American Physiological Society

Indexing

ISI Web of Knowledge - 91 Citations

Scopus - 115 Citations

Scientific classification

FOS: Medical and Health sciences > Clinical medicine

Other information

Authenticus ID: P-000-1ZC

DOI: 10.1152/ajpheart.01249.2004

Abstract (EN): 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 similar to 2-fold the expression of mitochondrial HSP-60 and tissue HSP-70 (P<0.05, n=10) and by similar to 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10