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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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Effects of NAC on urinary MeHg excretion in preweanling and adult rats treated with 0.1 μmol/kg [14C]MeHg 1 hr before treatment with 1 mmol/kg NAC. Values shown are amounts of [14C]MeHg excreted in urine 2 hr after NAC injection (mean ± SD); n = 4–5 rats per group.*Significantly different from adult animals (p < 0.05).
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f5-ehp0116-000026: Effects of NAC on urinary MeHg excretion in preweanling and adult rats treated with 0.1 μmol/kg [14C]MeHg 1 hr before treatment with 1 mmol/kg NAC. Values shown are amounts of [14C]MeHg excreted in urine 2 hr after NAC injection (mean ± SD); n = 4–5 rats per group.*Significantly different from adult animals (p < 0.05).

Mentions: Infants whose brains are still developing are at higher risk of MeHg poisoning (Clarkson 2002). Thus, it is important to determine whether NAC is effective in stimulating urinary excretion of MeHg in young animals. To test this possibility, we treated rats between 15–19 days of age with 0.1 μmol/kg MeHg iv, followed by a single dose of NAC 1 hr after MeHg injection. However, NAC administration had only minimal effects on urinary excretion of MeHg in the preweanling animals (Figure 5).


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

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

Effects of NAC on urinary MeHg excretion in preweanling and adult rats treated with 0.1 μmol/kg [14C]MeHg 1 hr before treatment with 1 mmol/kg NAC. Values shown are amounts of [14C]MeHg excreted in urine 2 hr after NAC injection (mean ± SD); n = 4–5 rats per group.*Significantly different from adult animals (p < 0.05).
© Copyright Policy - public-domain
Related In: Results  -  Collection

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

f5-ehp0116-000026: Effects of NAC on urinary MeHg excretion in preweanling and adult rats treated with 0.1 μmol/kg [14C]MeHg 1 hr before treatment with 1 mmol/kg NAC. Values shown are amounts of [14C]MeHg excreted in urine 2 hr after NAC injection (mean ± SD); n = 4–5 rats per group.*Significantly different from adult animals (p < 0.05).
Mentions: Infants whose brains are still developing are at higher risk of MeHg poisoning (Clarkson 2002). Thus, it is important to determine whether NAC is effective in stimulating urinary excretion of MeHg in young animals. To test this possibility, we treated rats between 15–19 days of age with 0.1 μmol/kg MeHg iv, followed by a single dose of NAC 1 hr after MeHg injection. However, NAC administration had only minimal effects on urinary excretion of MeHg in the preweanling animals (Figure 5).

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