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N-acetylcysteine as a potential antidote and biomonitoring agent of methylmercury exposure.

Aremu DA, Madejczyk MS, Ballatori N - Environ. Health Perspect. (2008)

Bottom Line: In contrast, NAC had no significant effect on urinary MeHg excretion in preweanling rats.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, 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.

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Related in: MedlinePlus

Effect of a standard dose of NAC (1 mmol/kg) on urinary excretion of [14C]MeHg. (A) Effect of NAC after treatment with various doses of [14C]MeHg (μmol/kg) over time. (B) Amount of [14C]MeHg excreted in urine 2 hr after NAC injection plotted against [14C]MeHg doses. (C) Actual amount of [14C]MeHg excreted in urine versus the amount injected; y = 16.133x + 0.0281; R2 = 0.9998. Values are mean ± SD; n = 4–5 rats in each group.
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f3-ehp0116-000026: Effect of a standard dose of NAC (1 mmol/kg) on urinary excretion of [14C]MeHg. (A) Effect of NAC after treatment with various doses of [14C]MeHg (μmol/kg) over time. (B) Amount of [14C]MeHg excreted in urine 2 hr after NAC injection plotted against [14C]MeHg doses. (C) Actual amount of [14C]MeHg excreted in urine versus the amount injected; y = 16.133x + 0.0281; R2 = 0.9998. Values are mean ± SD; n = 4–5 rats in each group.

Mentions: To test the hypothesis that a standardized dose of NAC will produce an increase in urinary MeHg excretion that is proportional to the body burden of MeHg, we treated animals with different doses of MeHg (0.01–1.0 μmol/kg), but all groups received a standard dose of 1.0 mmol/kg NAC at 2 hr after MeHg administration. The injection of NAC was followed by a sharp increase in urinary MeHg excretion at all MeHg doses (Figure 3A). Except for the lowest MeHg dose, the percentage excreted in the 2 hr following NAC injection was relatively constant, with a mean ± SD of 5.2 ± 0.3% of dose excreted over this time period (Figure 3B). When the amount of MeHg excreted in urine was plotted against the MeHg dose, we observed a linear relation (Figure 3C).


N-acetylcysteine as a potential antidote and biomonitoring agent of methylmercury exposure.

Aremu DA, Madejczyk MS, Ballatori N - Environ. Health Perspect. (2008)

Effect of a standard dose of NAC (1 mmol/kg) on urinary excretion of [14C]MeHg. (A) Effect of NAC after treatment with various doses of [14C]MeHg (μmol/kg) over time. (B) Amount of [14C]MeHg excreted in urine 2 hr after NAC injection plotted against [14C]MeHg doses. (C) Actual amount of [14C]MeHg excreted in urine versus the amount injected; y = 16.133x + 0.0281; R2 = 0.9998. Values are mean ± SD; n = 4–5 rats in each group.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2199271&req=5

f3-ehp0116-000026: Effect of a standard dose of NAC (1 mmol/kg) on urinary excretion of [14C]MeHg. (A) Effect of NAC after treatment with various doses of [14C]MeHg (μmol/kg) over time. (B) Amount of [14C]MeHg excreted in urine 2 hr after NAC injection plotted against [14C]MeHg doses. (C) Actual amount of [14C]MeHg excreted in urine versus the amount injected; y = 16.133x + 0.0281; R2 = 0.9998. Values are mean ± SD; n = 4–5 rats in each group.
Mentions: To test the hypothesis that a standardized dose of NAC will produce an increase in urinary MeHg excretion that is proportional to the body burden of MeHg, we treated animals with different doses of MeHg (0.01–1.0 μmol/kg), but all groups received a standard dose of 1.0 mmol/kg NAC at 2 hr after MeHg administration. The injection of NAC was followed by a sharp increase in urinary MeHg excretion at all MeHg doses (Figure 3A). Except for the lowest MeHg dose, the percentage excreted in the 2 hr following NAC injection was relatively constant, with a mean ± SD of 5.2 ± 0.3% of dose excreted over this time period (Figure 3B). When the amount of MeHg excreted in urine was plotted against the MeHg dose, we observed a linear relation (Figure 3C).

Bottom Line: In contrast, NAC had no significant effect on urinary MeHg excretion in preweanling rats.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, 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.

Show MeSH
Related in: MedlinePlus