| N-Acetylcysteine
as a Potential Antidote and Biomonitoring Agent of Methylmercury
Exposure David A. Aremu, Michael S. Madejczyk, and
Nazzareno Ballatori Department of Environmental Medicine,
University of Rochester School of Medicine, Rochester, New
York, USA Abstract
Background: Many people, by means of consumption of seafood or other anthropogenic sources, are exposed to levels of methylmercury (MeHg) that are generally considered to be quite low, but that may nevertheless produce irreversible brain damage, particularly in unborn babies. The only way to prevent or ameliorate MeHg toxicity is to enhance its elimination from the body. Objectives: Using N-acetylcysteine (NAC) , we aimed to devise a monitoring protocol for early detection of acute exposure or relatively low MeHg levels in a rodent model, and to test whether NAC reduces MeHg levels in the developing embryo. Results: NAC produced a transient, dose-dependent acceleration of urinary MeHg excretion in rats of both sexes. Approximately 5% of various MeHg doses was excreted in urine 2 hr after injection of 1 mmol/kg NAC. In pregnant rats, NAC markedly reduced the body burden of MeHg, particularly in target tissues such as brain, placenta, and fetus. In contrast, NAC had no significant effect on urinary MeHg excretion in preweanling rats. Conclusions: Because NAC causes a transient increase in urinary excretion of MeHg that is proportional to the body burden, it is promising as a biomonitoring agent for MeHg in adult animals. In view of this and because NAC is effective at enhancing MeHg excretion when given either orally or intravenously, can decrease brain and fetal levels of MeHg, has minimal side effects, and is widely available in clinical settings, NAC should be evaluated as a potential antidote and biomonitoring agent in humans. Keywords: N-acetylcysteine, antidote, biomarker, biomonitoring, embryotoxicity, methylmercury, toxicity. Environ Health Perspect 116:26–31 (2008) . doi:10.1289/ehp.10383 available via http://dx.doi.org/ [Online 17 October 2007]
Address correspondence to N. Ballatori, Department of Environmental Medicine, University of Rochester School of Medicine, 575 Elmwood Ave., Box EHSC, Rochester, NY 14642 USA. Telephone: (585) 275-0262. Fax: (585) 256-2591. E-mail: Ned_Ballatori@urmc.rochester.edu This work was supported in part by grants ES01247, ES07026, ES015965, ES06484, and DK48823 from the National Institutes of Health. The authors declare they have no competing financial interests. Received 19 April 2007 ; accepted 16 October 2007.
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