N-Acetylcysteine (NAC) is a derivative of the amino acid l-cysteine, which, previously, has been shown to protect against ethanol-induced apoptosis during early development.
Ongoing research demonstrates that NAC is also proving clinically beneficial in reducing oxidative stress–mediated lung, liver, and kidney damage, with protection likely resulting from a NAC-mediated increase in glutathione levels.
In the present study, the hypothesis that coadministration of NAC and ethanol by means of liquid diet on days 7 and 8 of pregnancy in mice would reduce ethanol's teratogenicity was tested.
For this work, adult nonpregnant female mice were acclimated to a liquid diet containing ethanol for 16 days, withdrawn from the ethanol, bred, and then returned to the liquid diet containing 4.8% ethanol and/or either 0.5 or 1-mg NAC/mL diet on their seventh and eighth days of pregnancy. At the concentrations used, the mice received NAC dosages of approximately 300 or 600 mg/kg/day and achieved peak blood ethanol concentrations (BEC) that averaged approximately 200 mg/dL.
There was no difference in BEC between the ethanol-alone and ethanol plus 600 mg/kg NAC group. After maternal euthanasia, gestational day (GD) 14 fetuses were removed, fixed, weighed, and examined for the presence and severity of ocular abnormalities, a readily assessed endpoint that results from GD 7 and 8 ethanol exposures.
Although the lower dosage of NAC (300 mg/kg) resulted in a decrease in the incidence of ocular defects in both the left and right eyes, this reduction was not statistically significant.
However, doubling the NAC concentration did yield a significant change; as compared with the group treated with ethanol alone, the incidence of ocular abnormalities was diminished by 22%.
These results show the potential of an orally administered compound with proven clinical efficacy to reduce ethanol's teratogenic effects and support the premise that oxidative damage plays an important mechanistic role in fetal alcohol spectrum disorders.
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Ongoing research demonstrates that NAC is also proving clinically beneficial in reducing oxidative stress–mediated lung, liver, and kidney damage, with protection likely resulting from a NAC-mediated increase in glutathione levels.
In the present study, the hypothesis that coadministration of NAC and ethanol by means of liquid diet on days 7 and 8 of pregnancy in mice would reduce ethanol's teratogenicity was tested.
For this work, adult nonpregnant female mice were acclimated to a liquid diet containing ethanol for 16 days, withdrawn from the ethanol, bred, and then returned to the liquid diet containing 4.8% ethanol and/or either 0.5 or 1-mg NAC/mL diet on their seventh and eighth days of pregnancy. At the concentrations used, the mice received NAC dosages of approximately 300 or 600 mg/kg/day and achieved peak blood ethanol concentrations (BEC) that averaged approximately 200 mg/dL.
There was no difference in BEC between the ethanol-alone and ethanol plus 600 mg/kg NAC group. After maternal euthanasia, gestational day (GD) 14 fetuses were removed, fixed, weighed, and examined for the presence and severity of ocular abnormalities, a readily assessed endpoint that results from GD 7 and 8 ethanol exposures.
Although the lower dosage of NAC (300 mg/kg) resulted in a decrease in the incidence of ocular defects in both the left and right eyes, this reduction was not statistically significant.
However, doubling the NAC concentration did yield a significant change; as compared with the group treated with ethanol alone, the incidence of ocular abnormalities was diminished by 22%.
These results show the potential of an orally administered compound with proven clinical efficacy to reduce ethanol's teratogenic effects and support the premise that oxidative damage plays an important mechanistic role in fetal alcohol spectrum disorders.
Read Full Abstract
Request Reprint E-Mail: sparnell@med.unc.edu
