N -Acetylcysteine treatment of dystrophic mdx mice results in protein thiol modifications and inhibition of exercise induced myofibre necrosis

Abstract 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 benef...

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Bibliographic Details
Published in:Neuromuscular disorders : NMD 2012-05, Vol.22 (5), p.427-434
Main Authors: Terrill, Jessica R, Radley-Crabb, Hannah G, Grounds, Miranda D, Arthur, Peter G
Format: Article
Language:English
Subjects:
Acetylcysteine - pharmacology
Animals
Antioxidants - pharmacology
Duchenne Muscular Dystrophy
Glutathione - metabolism
Male
mdx Mouse
Mice
Mice, Inbred C57BL
Mice, Inbred mdx
Muscle, Skeletal - metabolism
Muscle, Skeletal - pathology
Muscular Dystrophy, Animal - therapy
N-Acetylcysteine
Necrosis - prevention & control
Neurology
Oxidative Stress
Physical Conditioning, Animal
Protein Carbonylation
Protein thiol oxidation
Proteins - chemistry
Proteins - metabolism
Sulfhydryl Compounds - metabolism
Treadmill exercise
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Summary:Abstract 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.
ISSN:0960-8966
1873-2364
DOI:10.1016/j.nmd.2011.11.007