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 γ-glutamylcysteine synthetase, markedly enhanced (about 10-fold) the lethal and renal toxicity of mercuric chloride. The lethal toxicity of HgCl 2 was prevented by administration of GSH monoester; this was observed in mice pretreated with BSO and given a low dose of HgCl 2 and also in untreated mice that were given a much higher dose of HgCl 2. 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 HgCl 2 requires intracellular GSH. The experimental approaches used here suggest that cellular GSH is a major determinant of sensitivity to HgCl 2 toxicity, and also that administration of GSH esters may be useful for prevention of HgCl 2 toxicity.