Acute exercise protects against calcium-induced cardiac mitochondrial permeability transition pore opening in doxorubicin-treated rats

• Type: Article in International Scientific Journal
• Date: 2011

Authors

Antonio Ascensao (Author) FADEUP; Jose Lumini Oliviera (Author) Other; Nuno G Machado (Author) Other; Rita M Ferreira (Author) Other; Ines O Goncalves (Author) Other; Ana C Moreira (Author) Other; Franklin Marques (Author) FFUP; Vilma A Sardao (Author) Other; Paulo J Oliveira (Author) Other; Jose Magalhaes (Author) FADEUP

Journal

Title: Clinical Science

Vol. 120

Pages: 37-49

ISSN: 0143-5221

Publisher: PORTLAND PRESS LTD

Indexing

ISI Web of Knowledge - 52 Citations

Scopus - 69 Citations

Scientific classification

FOS: Medical and Health sciences > Other medical sciences

Other information

Authenticus ID: P-002-Y7J

DOI: 10.1042/cs20100254

Abstract (EN): The use of DOX (doxorubicin), an antibiotic used in oncological treatments, is limited by a dose-related cardiotoxicity against which acute exercise is protective. However, the mitochondrial-related mechanisms of this protection remain unknown. Therefore the present study aimed to determine the effects of an acute endurance exercise bout performed 24 h before DOX treatment on heart and liver mitochondrial function. A total of 20 adult male Wistar rats were divided into groups as follows: non-exercised with saline (NE + SAL), non-exercised DOX-treated (NE + DOX), exercised with saline (EX + SAL) and exercised DOX-treated (EX + DOX). The animals performed a 60 min exercise bout on a treadmill or remained sedentary 24 h before receiving either a DOX bolus (20 mg/kg of body weight) or saline. Heart and liver mitochondrial function [oxygen consumption, membrane potential (Delta psi) and cyclosporin-A-sensitive calcium-induced MPTP (mitochondrial permeability transition pore) opening) were evaluated. The activities of the respiratory complex, Mn-SOD (superoxide dismutase), caspases 3 and 9, as well as the levels of ANT (adenine nucleotide translocase), VDAC (voltage-dependent anion channel), CypD (cyclophilin D), Bax and Bcl-2, were measured. Acute exercise prevented the decreased cardiac mitochondrial function (state 3, phosphorylative lag-phase; maximal Delta psi generated both with complex I- and II-linked substrates and calcium-induced MPTP opening) induced by DOX treatment. Exercise also prevented the DOX-induced decreased activity of cardiac mitochondrial chain complexes I and V, and increased caspase 3 and 9 activities. DOX administration and exercise caused increased cardiac mitochondrial SOD activity. Exercise ameliorated liver mitochondrial complex activities. No alterations were observed in the measured MPTP and apoptosis-related proteins in heart and liver mitochondria. The results demonstrate that acute exercise protects against cardiac mitochondrial dysfunction, preserving mitochondrial phosphorylation capacity and attenuating DOX-induced decreased tolerance to MPTP opening.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13