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Concurrent Dietary Administration of D‐SAL and Ethanol Diminishes Ethanol’s Teratogenesis
Author(s) -
Parnell Scott E.,
Chen Shaoyu,
Charness Michael E.,
Hodge Clyde W.,
Dehart Deborah B.,
Sulik Kathleen K.
Publication year - 2007
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2007.00524.x
Subject(s) - ethanol , liquid diet , fetal alcohol syndrome , microphthalmia , endocrinology , medicine , alcohol , pathogenesis , fetus , oral administration , chemistry , pregnancy , biochemistry , biology , genetics , gene
Background: SAL (SALLRSIPA) is a peptide fragment of activity‐dependent neurotrophic factor. Both L‐ and D‐SAL diminish ethanol’s pathogenesis, however, the D‐peptide is protease resistant, and can therefore be effectively administered in a diet. The present study tested the hypothesis that D‐SAL provided in a liquid diet containing ethanol will prevent ethanol‐induced teratogenicity in mice. Methods: Following an ethanol acclimation period, female C57Bl/6J mice were withdrawn from the ethanol, bred, and then returned during gestational days (GD) 7 and 8 to a control liquid diet or one containing 4.8% ethanol alone or in combination with 5.6 μ g/ml D‐SAL. At these doses, the mice received approximately 75 μ g of D‐SAL on each day and achieved peak blood‐alcohol concentrations on GD 8 that ranged from 148–162 mg/dl. On GD 14, the fetuses were examined for the presence of ocular abnormalities including microphthalmia and irregularly shaped pupils, teratogenic effects known to result from this ethanol exposure paradigm. Results: Dietary D‐SAL reduced the incidence of ocular defects in ethanol‐exposed fetuses from 29 to 10% in the right eyes and from 21 to 7.5% in the left eyes; levels similar to those observed in pair‐fed controls. In addition to decreasing their incidence, D‐SAL also reduced the severity of the ocular defects. Conclusions: These results demonstrate that oral D‐SAL can prevent ethanol‐induced ocular defects. Because ocular defects are commonly associated with CNS damage, oral D‐SAL may also prove valuable in preventing ethanol‐induced brain defects.