Abstract

To evaluate age-dependent abnormalities in mitochondrial redox metabolism specifically in dystrophic skeletal muscle, oxygen consumption, thiobarbituric acid reactivity (TBARS), free-radical scavengers and oxidative marker enzymes were measured in the skeletal muscle from adult and senile control (C57BL/10) and dystrophic (mdx/+) mice. Mitochondrial oxygen consumption in state 3 was significantly lowered with age in the senile dystrophic (-52%) and less markedly in the senile control (-30%) skeletal muscle. Compared with adult muscle, mitochondrial concentration of TBARS and cellular concentration of lipofuscin were significantly increased in senile control and dystrophic muscle. Enzymatic activity of glutathione peroxidase (GSH-Px) and concentration of alpha-tocopherol were significantly increased in the senile control (GSH-Px 43+/-5.7 vs 53+/-8.7 U/g protein, alpha-tocopherol 0.19+/-0. 09 vs 0.29+/-0.14 micromol/g total lipids), but significantly decreased in the senile dystrophic (GSH-Px 80+/-8.0 vs 53+/-12 U/g protein, alpha-tocopherol 0.45+/-0.13 vs 0.19+/-0.03 micromol/g total lipids) muscle. Selenium content was significantly decreased only in senile dystrophic muscle (1.37+/-0.42 vs 0.78+/-0.21 nmol/g wet muscle). In conclusion, the enzymatic adaptation to reactive oxygen species was limited in the dystrophic skeletal muscle, suggesting a higher need for antioxidants, especially alpha-tocopherol.

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