OXIDATIVE STRESS AS A POTENTIAL PATHOGENIC MECHANISM IN AN ANIMAL-MODEL OF DUCHENNE MUSCULAR-DYSTROPHY

Dystrophin-deficiency results in degeneration of most, but not all, sk eletal muscles. The mechanisms responsible for degeneration of limb mu scle and sparing of extraocular muscle are not known. To address the n otion that muscle pathology may be free radical-mediated, we evaluated antioxidant enzyme activities and lipid peroxidation products (TEARS) content in mdx and control mice. TEARS content and the activities of total superoxide dismutase, selenium dependent glutathione peroxidase, glucose-6-phosphate dehydrogenase and catalase were consistently high er in both affected and spared muscles of mdx mice. These data suggest that oxidative stress may be constitutively present in mdx muscle, bu t may not be the principal pathogenic mechanism. To further test the h ypothesis of oxidative stress involvement in dystrophinopathies, contr ol strain and mdx mice were subjected to chronic hyperoxia. The patter n of antioxidant enzyme activities and TEARS content from hyperoxic co ntrol strain mice was similar to that of normoxic mdx mice, suggesting that a similar level of oxidative stress was induced. In conclusion, this study has provided indirect evidence for oxidative stress in dyst rophin-deficient muscle. (C) 1997 Elsevier Science B.V.