title: Cellular glutathione as a determinant of sensitivity to mercuric chloride toxicity. Prevention of toxicity by giving glutathione monoester.
abstract: Depletion of glutathione (GSH) by treatment of mice with buthionine sulfoximine (BSO), an effective inhibitor of gamma-glutamylcysteine synthetase, markedly enhanced (about 10-fold) the lethal and renal toxicity of mercuric chloride. The lethal toxicity of HgCl2 was prevented by administration of GSH monoester; this was observed in mice pretreated with BSO and given a low dose of HgCl2, and also in untreated mice that were given a much higher dose of HgCl2. In contrast, administration of GSH did not protect. Since administered GSH is not transported effectively into cells, whereas GSH monoester is transported and split intracellularly to GSH, the findings indicate that protection against HgCl2 requires intracellular GSH. The experimental approaches used here suggest that cellular GSH is a major determinant of sensitivity to HgCl2 toxicity, and also that administration of GSH esters may be useful for prevention of HgCl2 toxicity.
authors.affiliation: Department of Biochemistry, Cornell University Medical College, New York, NY 10021.
authors.forename: A
authors.initials: A
authors.lastname: Naganuma
authors.forename: M E
authors.initials: ME
authors.lastname: Anderson
authors.forename: A
authors.initials: A
authors.lastname: Meister
mesh_terms: D000818:Animals; D001806:Blood Urea Nitrogen; D019328:Buthionine Sulfoximine; D002104:Cadmium / Q000633:toxicity; D019256:Cadmium Chloride; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D008627:Mercuric Chloride / Q000633:toxicity*; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice
chemical_list: D002104:Cadmium; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D008627:Mercuric Chloride; C058293:glutathione monoisopropyl ester; D005978:Glutathione; D019256:Cadmium Chloride