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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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Effect of NAC on body burden and transplacental transfer of MeHg in pregnant rats. Residual levels of [14C]MeHg in selected organs (A) and in placentas and fetuses (B) from pregnant rats that received [14C]MeHg (0.1 μmol/kg) via lateral vein on GD14. After 24 hr, NAC-treated rats received 10 mg/mL NAC in their drinking water for 2 days. Values are mean ± SD; n = 4 rats in each group or 8 fetoplacental units from 4 rats in each group.*Significantly different from control (p < 0.05).
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f4-ehp0116-000026: Effect of NAC on body burden and transplacental transfer of MeHg in pregnant rats. Residual levels of [14C]MeHg in selected organs (A) and in placentas and fetuses (B) from pregnant rats that received [14C]MeHg (0.1 μmol/kg) via lateral vein on GD14. After 24 hr, NAC-treated rats received 10 mg/mL NAC in their drinking water for 2 days. Values are mean ± SD; n = 4 rats in each group or 8 fetoplacental units from 4 rats in each group.*Significantly different from control (p < 0.05).

Mentions: Because fetuses are exposed to MeHg via maternal blood and hence are prone to the danger of developmental abnormalities (Ornaghi et al. 1993), we determined the effectiveness of NAC in reducing the body burden of MeHg in pregnant dams. Pregnant dams were injected with MeHg via the lateral tail vein on GD14; 24 hr later some animals were supplied drinking water containing 10 mg/mL of NAC ad libitum for another 48 hr. Animals were then anesthetized, and we removed from each dam two fetoplacental units along with blood, liver, kidney, spleen, and brain for MeHg determination. The residual MeHg was significantly lower in the tissues isolated from the dams exposed to NAC in drinking water than in tissues from untreated dams, including the placenta and fetus (Figure 4A,B). NAC had different effects on individual tissue MeHg levels: blood and liver levels were decreased by approximately 60–80%, whereas kidney MeHg decreased by only 20%. In contrast, MeHg levels in the fetus and in placenta and maternal brain were decreased by approximately 70–90%.


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

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

Effect of NAC on body burden and transplacental transfer of MeHg in pregnant rats. Residual levels of [14C]MeHg in selected organs (A) and in placentas and fetuses (B) from pregnant rats that received [14C]MeHg (0.1 μmol/kg) via lateral vein on GD14. After 24 hr, NAC-treated rats received 10 mg/mL NAC in their drinking water for 2 days. Values are mean ± SD; n = 4 rats in each group or 8 fetoplacental units from 4 rats in each group.*Significantly different from control (p < 0.05).
© Copyright Policy - public-domain
Related In: Results  -  Collection

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

f4-ehp0116-000026: Effect of NAC on body burden and transplacental transfer of MeHg in pregnant rats. Residual levels of [14C]MeHg in selected organs (A) and in placentas and fetuses (B) from pregnant rats that received [14C]MeHg (0.1 μmol/kg) via lateral vein on GD14. After 24 hr, NAC-treated rats received 10 mg/mL NAC in their drinking water for 2 days. Values are mean ± SD; n = 4 rats in each group or 8 fetoplacental units from 4 rats in each group.*Significantly different from control (p < 0.05).
Mentions: Because fetuses are exposed to MeHg via maternal blood and hence are prone to the danger of developmental abnormalities (Ornaghi et al. 1993), we determined the effectiveness of NAC in reducing the body burden of MeHg in pregnant dams. Pregnant dams were injected with MeHg via the lateral tail vein on GD14; 24 hr later some animals were supplied drinking water containing 10 mg/mL of NAC ad libitum for another 48 hr. Animals were then anesthetized, and we removed from each dam two fetoplacental units along with blood, liver, kidney, spleen, and brain for MeHg determination. The residual MeHg was significantly lower in the tissues isolated from the dams exposed to NAC in drinking water than in tissues from untreated dams, including the placenta and fetus (Figure 4A,B). NAC had different effects on individual tissue MeHg levels: blood and liver levels were decreased by approximately 60–80%, whereas kidney MeHg decreased by only 20%. In contrast, MeHg levels in the fetus and in placenta and maternal brain were decreased by approximately 70–90%.

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