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标题：Effect of Fe-Overload on the Biotransformation of Methylmercury in Rat
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作者：AKIRA YASUTAKE ; TATSUMI ADACHI ; IKUO SUDA 等
期刊名称：Journal of Health Science
印刷版ISSN：1344-9702
电子版ISSN：1347-5207
出版年度：1993
卷号：39
期号：2
页码：106-113
DOI：10.1248/jhs1956.39.2_106
出版社：The Pharmaceutical Society of Japan
摘要：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 (CCl₄) treatment on the rate of biotransformation of MeHg was examined in rats. The effects of this treatment on H₂O₂-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 CCl₄ treatment, suggesting the effective production of ·OH. The CCl₄-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 CCl₄ 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 CCl₄ treatment may play a critical role in the biotransformation of MeHg in the liver.
关键词：methylmercury;demethylation;iron;reactive oxygen;rats