N-Acetylcysteine as an Antidote in Methylmercury Poisoning Nazzareno Ballatori,1 Michael W. Lieberman,2 and Wei Wang1 1Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642 USA
2Departments of Pathology and Cell Biology, Baylor College of Medicine, Houston, TX 77030 USA Abstract Methylmercury is a ubiquitous environmental pollutant and a potent neurotoxin. Treatment of methylmercury poisoning relies almost exclusively on the use of chelating agents to accelerate excretion of the metal. The present study demonstrates that oral administration of N-acetylcysteine (NAC) , a widely available and largely nontoxic amino acid derivative, produces a profound acceleration of urinary methylmercury excretion in mice. Mice that received NAC in the drinking water (10 mg/ml) starting at 48 hr after methylmercury administration excreted from 47 to 54% of the 203Hg in urine over the subsequent 48 hr, as compared to 4-10% excretion in control animals. When NAC-containing water was given from the time of methylmercury administration, it was even more effective at enhancing urinary methylmercury excretion and at lowering tissue mercury levels. In contrast, excretion of inorganic mercury was not affected by oral NAC administration. The ability of NAC to enhance methylmercury excretion when given orally, its relatively low toxicity, and its wide availability in the clinical setting indicate that it may be an ideal therapeutic agent for use in methylmercury poisoning. Key words: antidote, brain, glutathione, inorganic mercury, methylmercury, N-acetylcysteine, poisoning. Environ Health Perspect 106:267-271 (1998) . [Online 31 March 1998] http://ehpnet1.niehs.nih.gov/docs/1998/106p267-271ballatori/ abstract.html Address correspondence to N. Ballatori, Department of Environmental Medicine, Box EHSC, University of Rochester School of Medicine, 575 Elmwood Avenue, Rochester, NY 14642 USA. We thank Amy L. Wiseman for coordinating shipment of mice, Robert Gelein and Robert J. Baitchman for providing metabolic cages, Taft Toribara for synthesizing labeled methylmercury chloride, and Thomas W. Clarkson for cold-vapor atomic absorption analysis and for critically reviewing this manuscript. This research was supported in part by National Institutes of Health grants ES06484, ES07827, and DK48823, and NIEHS Center grant ES01247. Received 21 October 1997 ; accepted 12 January 1998. The full version of this article is available for free in HTML format. |