1989 Fiscal Year Final Research Report Summary
Studies on Mechanism of Neurotoxicity caused by Methylmercury
| Project/Area Number |
62480169
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hygiene
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| Research Institution | University of Tsukuba |
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Principal Investigator |
FUJIKI Motoo University of Tsukuba, Institute of Community Medicine, Professor, 社会医学系, 教授 (10040164)
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| Co-Investigator(Kenkyū-buntansha) |
KOIKE Kazuko University of Tsukuba, Institute of Community Medicine, Assistant Professor, 社会医学系, 講師 (60110508)
TAJIMA Shizuko University of Tsukuba, Institute of Community Medicine, Assistant Professor, 社会医学系, 講師 (50040192)
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| Project Period (FY) |
1987 – 1989
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| Keywords | Methylmercury / Oral administration / Mitochondria / Haemoglobin / Electron transfer chain / Glutathione / Minamata disease / Rat |
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| Research Abstract |
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.
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