N-Acetylcysteine treatment of dystrophic mdx mice results in protein thiol modifications and inhibition of exercise induced myofibre necrosis.
Oxidative stress is implicated as a factor that increases necrosis of skeletal muscles in Duchenne Muscular Dystrophy (DMD) and the dystrophic mdx mouse. Consequently, drugs that minimize oxidative stress are potential treatments for muscular dystrophy. This study examined the in vivo benefits to mdx mice of an antioxidant treatment with the cysteine precursor N-acetylcysteine (NAC), administered in drinking water. NAC was completely effective in preventing treadmill exercise-induced myofibre necrosis (assessed histologically) and the increased blood creatine kinase levels (a measure of sarcolemma leakiness) following exercise were significantly lower in the NAC treated mice. While NAC had no effect on malondialdehyde level or protein carbonylation (two indicators of irreversible oxidative damage), treatment with NAC for one week significantly decreased the oxidation of glutathione and protein thiols, and enhanced muscle protein thiol content. These data provide in vivo evidence for protective benefits of NAC treatment on dystropathology, potentially via protein thiol modifications.
School of Anatomy and Human Biology, The University of Western Australia, Crawley, Western Australia 6009, Australia.
Jessica R
JR
Terrill
Hannah G
HG
Radley-Crabb
Miranda D
MD
Grounds
Peter G
PG
Arthur
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009137:Muscular Dystrophy, Animal / Q000628:therapy*; D009336:Necrosis / Q000517:prevention & control; D018384:Oxidative Stress; D010805:Physical Conditioning, Animal; D050050:Protein Carbonylation; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D000975:Antioxidants; D011506:Proteins; D013438:Sulfhydryl Compounds; D005978:Glutathione; D000111:Acetylcysteine