N-acetylpenicillamine potentiated excretion of methyl mercury in rat bile: influence of S-methylcysteine.
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.
D000818:Animals; D001646:Bile / Q000032:analysis; D001652:Bile Ducts / Q000187:drug effects*; D002850:Chromatography, Gel; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004357:Drug Synergism; D005978:Glutathione / Q000378:metabolism; D007275:Injections, Intravenous; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008629:Mercury Isotopes; D008767:Methylmercury Compounds / Q000378:metabolism*; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D008629:Mercury Isotopes; D008767:Methylmercury Compounds; C010005:N-acetylpenicillamine; C008425:S-methylcysteine; D005978:Glutathione; D010396:Penicillamine; D003545:Cysteine; C004925:methylmercuric chloride