gamma-Glutamyltransferase-dependent biliary-hepatic recycling of methyl mercury in the guinea pig

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 262; no. 2; pp. 619 - 623
• Main Authors: Dutczak, W J, Ballatori, N
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.08.1992; American Society for Pharmacology and Experimental Therapeutics
• Subjects: Animals; Bile - metabolism; Biological and medical sciences; Chemical and industrial products toxicology. Toxic occupational diseases; Cysteine - metabolism; gamma-Glutamyltransferase - physiology; Glutathione - metabolism; Guinea Pigs; Isoxazoles - pharmacology; Liver - metabolism; Male; Medical sciences; Metals and various inorganic compounds; Methylmercury Compounds - metabolism; Toxicology; Biliary tract; Cysteine; Intravenous administration; Enzyme; Digestive system; Secretion; Liver; Rodentia; Glycine; Metabolism; γ-Glutamyltransferase; Vertebrata; Dipeptidase; Mammalia; Guinea pig; Animal; Glutathione
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1016/S0022-3565(25)10803-3

After secretion into bile, glutathione (GSH) and GSH-conjugates are catabolized by gamma-glutamyltransferase (gamma-GT) and dipeptidases yielding glutamate, cysteine, glycine and cysteine S-conjugates, and these products are then partially reabsorbed from the biliary tree. Because methyl mercury is thought to be secreted into bile as a GSH- complex, it may be subject to a similar intrahepatic cycle, thus delaying its elimination. To examine this possibility guinea pigs were dosed with 203Hg-methyl mercury (10 mumol/kg i.v.), followed by a retrograde intrabiliary infusion of Krebs-Henseleit buffer (control) or acivicin (an inhibitor of gamma-GT). Acivicin increased biliary excretion of 203Hg by 41%, and GSH from 0.14 +/- 0.10 to 2.02 +/- 0.26 nmol/min.g of liver. Bile analyzed by gel filtration chromatography revealed that CH(3)203Hg-GSH accounted for most of this increased 203Hg excretion. When CH(3)203Hg-complexes of GSH, cysteine and albumin were introduced directly into the biliary tree by retrograde infusion, 203Hg recovery in bile was significantly lower than recovery of the nonabsorbable marker [14C]sucrose, ranging from 26.0 +/- 2.9% for CH(3)203Hg-cysteine to 48.7 +/- 5.1% for CH(3)203Hg-albumin and approximately 60% for [14C]sucrose. Acivicin pretreatment significantly increased 203Hg excretion into bile after retrograde infusion of CH(3)203Hg-GSH, whereas 203Hg recovery after retrograde infusion of CH(3)203Hg-cysteine remained constant.