School of Anatomy and Human Biology, The University of Western Australia, Crawley, Western Australia 6009, Australia.
Neuromuscul Disord. 2012 May;22(5):427-34. doi: 10.1016/j.nmd.2011.11.007. Epub 2011 Dec 27.
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.
氧化应激被认为是增加杜氏肌营养不良症 (DMD) 和肌营养不良症 mdx 小鼠骨骼肌坏死的一个因素。因此，最小化氧化应激的药物是肌肉疾病的潜在治疗方法。本研究通过在饮用水中给予半胱氨酸前体 N-乙酰半胱氨酸 (NAC) 的抗氧化治疗，检查了 mdx 小鼠的体内益处。NAC 完全有效预防了跑步机运动引起的肌纤维坏死（通过组织学评估），并且在 NAC 处理的小鼠中，运动后血液肌酸激酶水平（肌细胞膜通透性的衡量标准）显著降低。虽然 NAC 对丙二醛水平或蛋白质羰基化（两种不可逆氧化损伤的指标）没有影响，但 NAC 治疗一周可显著降低谷胱甘肽和蛋白质巯基的氧化，并增强肌肉蛋白质巯基含量。这些数据为 NAC 治疗对营养不良病理的保护益处提供了体内证据，可能是通过蛋白质巯基修饰。
