In vivo protection of a water-soluble derivative of vitamin E, Trolox, against methylmercury-intoxication in the rat
In vivo protection of a water-soluble derivative of vitamin E, Trolox, against methylmercury-intoxication in the rat
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DOI：
10.1016/s0304-3940(01)01764-5
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发表时间：
2001-05-25
影响因子：
2.5
通讯作者：
Higuchi, I
中科院分区：
文献类型：
--
作者：
Usuki, F;Yasutake, A;Higuchi, I
甲基汞（MeHg）是一种众所周知的神经毒物。甲基汞中毒会导致骨骼肌线粒体能量代谢紊乱和小脑细胞凋亡。我们报告了抗氧化剂 Trolox（6-羟基-2,5,7,8-四甲基苯并二氢吡喃-2-羧酸）（一种水溶性维生素 E 类似物）首次在体内有效对抗甲基汞诱导的细胞反应。尽管保留了甲基汞，但用Trolox（6-羟基-2.5,7,8-四甲基苯并二氢吡喃-2-羧酸）治疗可明显保护经甲基汞处理的大鼠骨骼肌，防止线粒体电子传递系统酶活性下降。 Tdt 介导的 dUTP 缺口末端标记方法阐明 Trolox 可有效保护小脑免受甲基汞诱导的细胞凋亡。这些数据表明，甲基汞介导的氧化应激在甲基汞中毒的体内病理过程中发挥着重要作用。 Trolox 可以预防人类甲基汞中毒的一些临床表现。 (C) 2001 Elsevier Science Ireland Ltd. 保留所有权利。
Methylmercury (MeHg) is a well-known neurotoxicant. MeHg-intoxication causes a disturbance in mitochondrial energy metabolism in skeletal muscle and apoptosis in cerebellum. We report the first in vivo effectiveness of antioxidant Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), a water soluble vitamin E analog, against the MeHg-induced cellular responses. Treatment with Trolox (6-hydroxy-2.5,7,8-tetramethylchroman-2-carboxylic acid) clearly protects MeHg-treated rat skeletal muscle against the decrease in mitochondrial electron transport system enzyme activities despite the retention of MeHg. Tdt-mediated dUTP nick-end-labeling method clarified that Trolox is effective for protecting cerebellum from MeHg-induced apoptosis. These data indicate that MeHg-mediated oxidative stress plays an important role in the in vivo pathological process of MeHg intoxication. Trolox may prevent some of clinical manifestations of MeHg-intoxication in humans. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.