Sutphin M S, Buckman T D
Division of Nutritional Sciences, UCLA School of Public Health 90024.
Neurochem Res. 1991 Dec;16(12):1257-63. doi: 10.1007/BF00966655.
To investigate the role of chronic oxidative stress in MPTP neurotoxicity, C57BL mice were maintained 6-8 weeks on diets deficient in nutrients essential to cellular antioxidant defenses, selenium (Se) and alpha-tocopherol (vit E), and the effects on tissue antioxidant status and MPTP toxicity were evaluated relative to controls on supplemented diets. Activities of the major antioxidant enzymes, glutathione peroxidase (GPx), catalase, and superoxide dismutase, and levels of malondialdehyde as a marker for oxidative stress, were measured in brain, lung, liver and blood. Caudate depletion of dopamine and its metabolites served as a measure of MPTP neurotoxicity. For mice on the Se deficient diet, levels of the selenoenzyme GPx decreased from 50% in brain to 90% in blood. No compensatory changes in the activities of the other antioxidant enzymes were observed and addition of vit E to the diet did not alter antioxidant enzyme activities or malondialdehyde levels. In animals not treated with MPTP, the Se deficient diet significantly increased malondialdehyde only in liver. No protective effect of the antioxidant supplements against caudate depletion of dopamine and its metabolites were observed. However, malondialdehyde levels were increased in the brains of MPTP treated mice on the low Se diets, suggesting the possibility of secondary oxidative damage to tissues accompanying the destruction of substantia nigra neurons by MPTP.
为了研究慢性氧化应激在MPTP神经毒性中的作用，将C57BL小鼠在缺乏细胞抗氧化防御必需营养素硒（Se）和α-生育酚（维生素E）的饮食上饲养6 - 8周，并相对于补充饮食的对照组评估其对组织抗氧化状态和MPTP毒性的影响。在脑、肺、肝和血液中测量了主要抗氧化酶谷胱甘肽过氧化物酶（GPx）、过氧化氢酶和超氧化物歧化酶的活性，以及作为氧化应激标志物的丙二醛水平。尾状核中多巴胺及其代谢产物的消耗作为MPTP神经毒性的指标。对于食用缺硒饮食的小鼠，硒酶GPx的水平从脑中的50%降至血液中的90%。未观察到其他抗氧化酶活性的代偿性变化，并且在饮食中添加维生素E也未改变抗氧化酶活性或丙二醛水平。在未用MPTP处理的动物中，缺硒饮食仅在肝脏中显著增加了丙二醛。未观察到抗氧化剂补充剂对尾状核中多巴胺及其代谢产物消耗的保护作用。然而，在低硒饮食的MPTP处理小鼠的脑中，丙二醛水平升高，这表明在MPTP破坏黑质神经元的同时，组织可能存在继发性氧化损伤。
