Department of Neuroscience, Neurological Clinic, University of Pisa, Via Roma 67, 56126 Pisa, Italy.
J Neurol. 2010 May;257(5):774-81. doi: 10.1007/s00415-009-5409-7. Epub 2009 Dec 4.
Mitochondrial diseases are due to impairment of the mitochondrial respiratory chain. A plausible pathogenic mechanism leading to cellular dysfunction and phenotypic expression is oxidative stress, but there are surprisingly few clinical studies on this subject. Glutathione (GSH) deficiency has been reported in mitochondrial diseases, and the biosynthesis of glutathione depends on cysteine availability. We have examined oxidative stress biomarkers [advanced oxidation protein products (AOPP) and ferric reducing antioxidant power (FRAP)] in blood samples from 27 patients and 42 controls. AOPP levels were greater in patients than in controls (P value <0.00001). Therefore, we performed a double-blind cross-over study to evaluate if 30-day supplementation with a whey-based cysteine donor could modify these markers, reduce lactate concentration during aerobic exercise, or enhance muscular strength and quality of life. Treatment did not modify lactate concentration, clinical scale (MRC) or quality of life (SF-36), but significantly reduced oxidative stress levels. Our findings reinforce the notions that in mitochondrial diseases oxidative stress is important and can be reduced by administration of a cysteine donor. Oxidative stress biomarkers may be useful to detect redox imbalance in mitochondrial diseases and to provide non-invasive tools to monitor disease status.
线粒体疾病是由于线粒体呼吸链的损伤引起的。一个合理的致病机制导致细胞功能障碍和表型表达是氧化应激，但在这个主题上，临床研究却少之又少。已有研究报道线粒体疾病存在谷胱甘肽（GSH）缺乏，而谷胱甘肽的生物合成依赖于半胱氨酸的可用性。我们检测了 27 名患者和 42 名对照者的血液样本中的氧化应激生物标志物[晚期氧化蛋白产物（AOPP）和铁还原抗氧化能力（FRAP）]。与对照组相比，患者的 AOPP 水平更高（P 值<0.00001）。因此，我们进行了一项双盲交叉研究，以评估 30 天补充乳清基半胱氨酸供体是否可以改变这些标志物，降低有氧运动期间的乳酸浓度，或增强肌肉力量和生活质量。治疗并未改变乳酸浓度、临床量表（MRC）或生活质量（SF-36），但显著降低了氧化应激水平。我们的研究结果证实了氧化应激在线粒体疾病中很重要的观点，并且可以通过给予半胱氨酸供体来减轻。氧化应激生物标志物可能有助于检测线粒体疾病中的氧化还原失衡，并提供非侵入性工具来监测疾病状态。
