Biliary-hepatic recycling of a xenobiotic: gallbladder absorption of methyl mercury.
The role of the gallbladder in the disposition of methyl mercury was investigated in guinea pig, hamster, and macaque monkey. 203Hg-labeled methyl mercury or inorganic mercury (5 microM) and [14C]inulin were instilled into the in situ guinea pig or hamster gallbladder. After 2 h, only 27.6 +/- 7.0% of the methyl mercury remained in guinea pig gallbladder fluid as compared with 85.0 +/- 3.2% of the inorganic mercury and 90.7 +/- 4.5% of the [14C]-inulin. In the hamster, 42.5 +/- 4.5% of methyl mercury and 95% +/- 0.9% of inorganic mercury remained after 2 h. When the sulfhydryl-containing compounds L-cysteine, glutathione, and bovine serum albumin (20 microM) were added to the test solution, cysteine increased and albumin decreased absorption of methyl mercury. Ligation of guinea pig cystic artery decreased gallbladder fluid absorption from 72.7 +/- 8.6 to 26.5 +/- 9.8% over 2 h but did not alter methyl mercury absorption. Bile was also sampled from gallbladders of four monkeys exposed chronically to CH3HgCl and from three control monkeys. For one of the exposed and one of the control monkeys, bile was also collected from the common hepatic duct. In both methyl mercury-exposed and control monkeys, the concentration of methyl mercury in gallbladder bile was lower than in hepatic bile. In contrast, the concentration of inorganic mercury in gallbladder bile was four to seven times that of hepatic bile, suggesting that methyl mercury but not inorganic mercury was being reabsorbed. To assess the functional significance of methyl mercury reabsorption by the gallbladder, guinea pig cystic ducts were ligated, the animals were given CH3 203HgCl (10 mumol/kg iv), and body burden of 203Hg was measured over 16 days.(ABSTRACT TRUNCATED AT 250 WORDS)
Dutczak
W J
WJ
Department of Biophysics, University of Rochester School of Medicine, New York 14642.
Clarkson
T W
TW
Ballatori
N
N
D000042:Absorption; D000818:Animals; D001652:Bile Ducts / Q000502:physiology; D006224:Cricetinae; D005704:Gallbladder / Q000187:drug effects / Q000502:physiology*; D006168:Guinea Pigs; D008658:Inactivation, Metabolic; D008099:Liver / Q000502:physiology*; D008251:Macaca; D008297:Male; D008627:Mercuric Chloride / Q000378:metabolism / Q000493:pharmacokinetics; D008631:Mercury Radioisotopes; D008647:Mesocricetus; D008767:Methylmercury Compounds / Q000378:metabolism* / Q000493:pharmacokinetics; D011865:Radioisotope Dilution Technique; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D015262:Xenobiotics / Q000378:metabolism*
D008631:Mercury Radioisotopes; D008767:Methylmercury Compounds; D013438:Sulfhydryl Compounds; D015262:Xenobiotics; D008627:Mercuric Chloride