Studies on Mechanism of Neurotoxicity caused by Methylmercury

甲基汞神经毒性机制研究

• 批准号: 62480169
• 负责人: FUJIKI Motoo
• 金额: $ 3.9万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-62480169/
• 关键词: Methylmercury; Oral administration; Mitochondria; Haemoglobin; Electron transfer chain; Glutathione; Minamata disease; Rat; ヘモグロビン; シナプトソ-ム; チトクロ-ム; 差スペクトル; システイン; 非結合型メチル水銀; チトロクロム; 塩化メチル水銀; メチル水銀中毒モデル; ミトコンドリア呼吸能; チトクロムC; 差スペクトル法

In this study, the pharmacokinetics of methylmercury(MM) in rat and its effects on brain mitochondria of rats with the subacute toxicity caused by oral methylmercury chloride administration were investigated.Oral administration of methylmercury chloride to rat by a stomach tube for 7days at a daily dose of 7.0-8.5mg (as Hg/kg rat weight) induced toxicity symptoms of paralysis and hind limb ataxia.The results revealed that MM is tightly bound to haemoglobin in the blood. Moreover a possibility was suggested that the MM in the blood formed a complex with the sulfhydryl group of glutathione(GSH), namely GSH-MM complex, and which is then transferred to several organs. It was also suggested that lipid-soluble MM is related with the translocation into the brain,the accumulation in the brain and the excretion from the brain. The effects of MM on sitochondrial respiration in vitro and in vivo was also studied. In vitro,it was indicated that MM reversely inhibited,the process of oxidative phosphorylation, and that the inhibitory site was located in the electron transfer chain between flavin and cytochrome c_1. In vivo,the MM inhibition on the mitochondria was not observed remarkably,however,lipid peroxidation might occur in the synaptosomal fraction.This study evidently showed that orally administered MM has several biochemical effects on the cellular level.

在本研究中，本文研究了氯化甲基汞（methylmercury，MM）在大鼠体内的药代动力学及其对大鼠脑线粒体的影响。大鼠经胃管灌胃氯化甲基汞7.0-8.5mg，连续7天结果表明，MM与血液中的血红蛋白紧密结合。此外，还提出了一种可能性，即血液中的MM与谷胱甘肽（GSH）的巯基形成复合物，即GSH-MM复合物，然后转移到多个器官。脂溶性MM与其在脑内的转运、蓄积和排泄有关。本文还研究了MM在体内外对线粒体呼吸的影响。在体外实验中，MM-1抑制氧化磷酸化过程，其抑制部位位于黄素与细胞色素c_1之间的电子传递链上。在体内，MM对线粒体的抑制作用不明显，但在突触体部分可能发生脂质过氧化反应，这表明口服MM在细胞水平上具有多种生化作用。