Effect of Fe-Overload on the Biotransformation of Methylmercury in Rat

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概要

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• It is well documented that methylmercury (MeHg) in vivo slowly undergoes demethylation reaction to change to inorganic mercury (Hg-i). The cleavage of the C-Hg bond was suggested to occur via a reactive oxygen-mediated process in vitro. To study the possibility of the involvement of hydroxyl radical (・OH) in the demethylation of MeHg in vivo, the combined effect of Fe-overload and carbon tetrachloride (CCl_4) treatment on the rate of biotransformation of MeHg was examined in rats. The effects of this treatment on H_2O_2-scavenging enzyme activities (catalase and glutathione peroxidase) were also studied. Rats were fed 3.5% Fe (II) fumalate-containing diet for 0,7 or 21 d to load Fe. Feeding of the Fe-containing diet brought about a time-dependent increase of the hepatic Fe levels by nearly 7-fold after 3 weeks. The serum Fe levels showed a maximum on day 7,while the renal levels increased after day 7. TBA-reactive substance levels in the liver significantly increased along with the Fe feeding, and this increase was drastically accelerated by CCl_4 treatment, suggesting the effective production of ・OH. The CCl_4-induced stimulation of the lipid peroxidation was observed also in serum and kidney, though not as marked as in the liver. The hepatic accumulations of total and inorganic Hg at 72 h after MeHg administration were significantly increased by the Fe-feeding. The proportion of Hg-i to total Hg in this tissue increased markedly by the combined effect of Fe and CCl_4 with the concomitant decrease of catalase activity. On the other hand, the renal accumulation of Hg-i drastically decreased by the Fe-load, while the MeHg levels remained unchanged. Since the renal metallothionein levels were found to be lowered after the Fe-feeding, this might account for the reduced retention of Hg-i in the whole kidney. The present results suggest that reactive oxygen species, probably ・OH, induced by Fe and CCl_4 treatment may play a critical role in the biotransformation of MeHg in the liver.

• 社団法人日本薬学会の論文
• 1993-04-30

著者

• 須田 郁夫

  農林水産省九州農業試験場

• 安武 章

  国立水俣病総合研究センター

• 平山 紀美子

  Kumamoto University College Of Medical Science

• 足立 達美

  Biochemistry Section, Department of Basic Medical Sciences, National Institute for Minamata Disease

• 安武 章

  Biochemistry Section, Department of Basic Medical Sciences, National Institute for Minamata Disease

• 須田 郁夫

  Kyushu National Agricultural Experiment Station

• 足立 達美

  Biochemistry Section Department Of Basic Medical Sciences National Institute For Minamata Disease

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