Refsvik T
Acta Pharmacol Toxicol (Copenh). 1984 Aug;55(2):121-5. doi: 10.1111/j.1600-0773.1984.tb01973.x.
N-acetylpenicillamine, 5 mmol/kg body weight increased biliary excretion of methyl mercury more than three fold. Upon simultaneous administration of the same dose of N-acetylpenicillamine and 2,5 mmol/kg body weight of S-methylcysteine biliary excretion of methyl mercury increased only 1.5 fold. In both cases biliary sulfhydryl concentration increased to the same extent, about 5 fold. Decreased biliary excretion of methyl mercury, as a result of liver depletion of reduced glutathione by cyclohexene oxide, could be restored by N-acetylpenicillamine. This restoration could be depressed by S-methylcysteine. The experiments undertaken indicate that N-acetylpenicillamine potentiated methyl mercury excretion occurs by a glutathione S-transferase dependent mechanism. Bile, collected after successive administration of methyl mercuric chloride, cyclohexene oxide, S-methylcysteine and N-acetylpenicillamine contained the methyl mercuric derivatives of N-acetylpenicillamine and glutathione together with other methyl mercury carrying components not present in control bile. Whether these components play any role in the mechanism of N-acetylpenicillamine potentiated methyl mercury excretion cannot be stated from the present investigation.
N - 乙酰青霉胺，5 mmol/kg体重可使甲基汞的胆汁排泄增加三倍多。当同时给予相同剂量的N - 乙酰青霉胺和2.5 mmol/kg体重的S - 甲基半胱氨酸时，甲基汞的胆汁排泄仅增加1.5倍。在这两种情况下，胆汁中巯基浓度均增加到相同程度，约为5倍。由于环己烯氧化物使肝脏中还原型谷胱甘肽耗竭导致甲基汞胆汁排泄减少，可通过N - 乙酰青霉胺恢复。这种恢复可被S - 甲基半胱氨酸抑制。所进行的实验表明，N - 乙酰青霉胺增强甲基汞排泄是通过谷胱甘肽S - 转移酶依赖性机制发生的。在连续给予甲基氯化汞、环己烯氧化物、S - 甲基半胱氨酸和N - 乙酰青霉胺后收集的胆汁中，含有N - 乙酰青霉胺和谷胱甘肽的甲基汞衍生物以及对照胆汁中不存在的其他携带甲基汞的成分。从目前的研究尚无法说明这些成分在N - 乙酰青霉胺增强甲基汞排泄的机制中是否起任何作用。
