title: Oxidative stress as a potential pathogenic mechanism in an animal model of Duchenne muscular dystrophy.
abstract: Dystrophin-deficiency results in degeneration of most, but not all, skeletal muscles. The mechanisms responsible for degeneration of limb muscle and sparing of extraocular muscle are not known. To address the notion that muscle pathology may be free radical-mediated, we evaluated antioxidant enzyme activities and lipid peroxidation products (TBARS) content in mdx and control mice. TBARS content and the activities of total superoxide dismutase, selenium dependent glutathione peroxidase, glucose-6-phosphate dehydrogenase and catalase were consistently higher in both affected and spared muscles of mdx mice. These data suggest that oxidative stress may be constitutively present in mdx muscle, but may not be the principal pathogenic mechanism. To further test the hypothesis of oxidative stress involvement in dystrophinopathies, control strain and mdx mice were subjected to chronic hyperoxia. The pattern of antioxidant enzyme activities and TBARS content from hyperoxic control 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 dystrophin-deficient muscle.
authors.affiliation: Department of Anatomy and Neurobiology, University of Kentucky, Lexington 40536-0084, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Ragusa
authors.forename: C K
authors.initials: CK
authors.lastname: Chow
authors.forename: J D
authors.initials: JD
authors.lastname: Porter
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism; D016189:Dystrophin / Q000172:deficiency / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D018496:Hyperoxia / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000378:metabolism; D009137:Muscular Dystrophy, Animal / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology*; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D016189:Dystrophin; D017392:Thiobarbituric Acid Reactive Substances; D005954:Glucosephosphate Dehydrogenase; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase