Burns David P, Ali Izza, Rieux Clement, Healy James, Jasionek Greg, O'Halloran Ken D
Department of Physiology, University College Cork, Western Gateway Building, Western Road, Cork T12 XF62, Ireland.
Antioxidants (Basel). 2017 Dec 6;6(4):101. doi: 10.3390/antiox6040101.
Duchenne muscular dystrophy (DMD) is characterized by striated muscle weakness, cardiomyopathy, and respiratory failure. Since oxidative stress is recognized as a secondary pathology in DMD, the efficacy of antioxidant intervention, using the superoxide scavenger tempol, was examined on functional and biochemical status of dystrophin-deficient diaphragm muscle. Diaphragm muscle function was assessed, ex vivo, in adult male wild-type and dystrophin-deficient mice, with and without a 14-day antioxidant intervention. The enzymatic activities of muscle citrate synthase, phosphofructokinase, and lactate dehydrogenase were assessed using spectrophotometric assays. Dystrophic diaphragm displayed mechanical dysfunction and altered biochemical status. Chronic tempol supplementation in the drinking water increased diaphragm functional capacity and citrate synthase and lactate dehydrogenase enzymatic activities, restoring all values to wild-type levels. Chronic supplementation with tempol recovers force-generating capacity and metabolic enzyme activity in diaphragm. These findings may have relevance in the search for therapeutic strategies in neuromuscular disease.
杜兴氏肌肉营养不良症（DMD）的特征是横纹肌无力、心肌病和呼吸衰竭。由于氧化应激被认为是DMD的继发性病理，因此使用超氧化物清除剂tempol进行抗氧化干预对肌营养不良蛋白缺乏的膈肌功能和生化状态的疗效进行了研究。在成年雄性野生型和肌营养不良蛋白缺乏的小鼠中，在有和没有14天抗氧化干预的情况下，离体评估膈肌功能。使用分光光度法测定肌肉柠檬酸合酶、磷酸果糖激酶和乳酸脱氢酶的酶活性。营养不良的膈肌表现出机械功能障碍和生化状态改变。在饮用水中长期补充tempol可提高膈肌功能能力以及柠檬酸合酶和乳酸脱氢酶的酶活性，使所有值恢复到野生型水平。长期补充tempol可恢复膈肌的力量生成能力和代谢酶活性。这些发现可能与寻找神经肌肉疾病的治疗策略有关。
