Physiological model for the pharmacokinetics of methyl mercury in the growing rat.
Physiological model for the pharmacokinetics of methyl mercury in the growing rat.
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DOI：
10.1006/taap.1993.1046
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发表时间：
1993-03
影响因子：
3.8
通讯作者：
F. Farris;R. Dedrick;P. Allen;J. C. Smith
中科院分区：
文献类型：
--
作者：
F. Farris;R. Dedrick;P. Allen;J. C. Smith
本文描述了甲基汞及其代谢产物汞在生长期大鼠体内的生理药代动力学模型。宿主组织和胃肠道植物群似乎都发生了脱甲基作用，无机汞的胆汁分泌和甲基汞进入肠腔的转运以及随后的大量细菌代谢是其消除的主要途径。有机和无机汞的胆汁转运是根据已知的谷胱甘肽从肝池的分泌来模拟的。在98天后，口服示踪剂剂量的203汞标记的氯化甲基汞，65%的管理剂量已被回收的粪便中的无机汞和15%的有机汞。尿液排泄是次要的消除途径，甲基汞的排泄量不到4%，无机汞的排泄量不到1%。汞剂不可逆地进入头发是一种重要的消除途径。在98天期间，10%的给药剂量包含在脱落的毛发中，在该时间段结束时，超过12%的剂量（几乎90%的身体负荷）保留在毛发中。梳理期间大鼠明显摄入毛发代表了一种新形式的毒素再循环。两种化学物质在血液和组织之间的运输是双向和对称的，进出大脑的运动相对缓慢。两种汞的运输机制进行了讨论的毛细血管运输生理学和血脑屏障的小分子和蛋白质。
We describe a physiological pharmacokinetic model for methyl mercury and its metabolite mercuric mercury in the growing rat. Demethylation appears to occur in both host tissues and gastrointestinal flora with elimination dominated by biliary secretion of inorganic mercury and by transport of methyl mercury into the gut lumen followed by substantial bacterial metabolism. Biliary transport of both organic and inorganic mercury is modeled in terms of the known secretion of glutathione from the hepatic pool. At 98 days following an oral tracer dose of 203Hg-labeled methyl mercury chloride, 65% of the administered dose had been recovered in the feces as inorganic mercury and 15% as organic mercury. Urinary excretion is a minor elimination route, accounting for less than 4% of the dose as methyl mercury and 1% of the dose as inorganic mercury. Irreversible incorporation of the mercurials into hair is a significant route of elimination. Ten percent of the administered dose was contained in the hair shed during the 98 days and over 12% of the dose (almost 90% of the body burden) remained in the hair at the end of that time period. Apparent ingestion of hair by the rats during grooming represents a novel form of toxin recirculation. Transport of both chemical species between blood and tissues is bidirectional and symmetric with relatively slow movement into and out of the brain. Transport mechanisms for both mercurial species are discussed in the context of capillary transport physiology and the blood-brain barrier to small molecules and proteins.