Relationships between alterations in glutathione metabolism and the disposition of inorganic mercury in rats: effects of biliary ligation and chemically induced modulation of glutathione status

Influences of biliary ligation and systemic depletion of glutathione (GSH) or modulation of GSH status on the disposition of a low, non-nephrotoxic i. v. dose of inorganic mercury were evaluated in rats in the present study. R enal and hepatic disposition, and the urinary and fecal excretion, of inorg anic mercury were assessed 24 h after the injection of a 0.5-mu mol/kg dose of mercuric chloride in control rats and rats pretreated with acivicin (tw o 10-mg/kg i.p. doses in 2 ml/kg normal saline, 90 min apart, 60 min before mercuric chloride), buthionine sulfoximine (BSO; 2 mmol/kg i.v. in 4 ml/kg normal saline, 2 h before mercuric chloride) or diethylmaleate (DEM; 3.37 mmol/kg i.p. in 2 ml/kg corn oil, 2 h before mercuric chloride) that either underwent or did not undergo acute biliary ligation prior to the injection of mercury. Among the groups that did not undergo biliary ligation, the pr etreatments used to alter GSH status systemically had varying effects on th e disposition of inorganic mercury in the kidneys, liver, and blood. Biliar y ligation caused the net renal accumulation of mercury to decrease under a ll pretreatment conditions. By contrast, biliary ligation caused significan t increases in the hepatic burden of mercury in all pretreatment groups exc ept in the acivicin-pretreated group. Blood levels of mercury also increase d as a result of biliary ligation, regardless of the type of pretreatment u sed. The present findings indicate that biliary ligation combined with meth ods used to modulate GSH status systemically have additive effects with res pect to causing reductions in the net renal accumulation of mercury. Additi onally, the findings indicate that at least some fraction of the renal accu mulation of inorganic mercury is linked mechanistically to the hepato-bilia ry system. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.