Concurrent dietary administration of D-SAL and ethanol diminishes ethanol's teratogenesis.
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Following an ethanol acclimation period, female C57Bl/6J mice were withdrawn from the ethanol, bred, and then returned during gestational days (GD) 7 and 8 to a control liquid diet or one containing 4.8% ethanol alone or in combination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 microg/ml D-SAL. At these doses, the mice received approximately 75 microg 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.
Parnell
Scott E
SE
Bowles Center for Alcohol Studies, Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA. sparnell@med.unc.edu
Chen
Shao-yu
SY
Charness
Michael E
ME
Hodge
Clyde W
CW
Dehart
Deborah B
DB
Sulik
Kathleen K
KK
D000818:Animals; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000037:antagonists & inhibitors* / Q000097:blood / Q000633:toxicity*; D005124:Eye Abnormalities / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000209:etiology / Q000517:prevention & control*; D015994:Incidence; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009479:Neuropeptides; D009842:Oligopeptides; D010446:Peptide Fragments / Q000494:pharmacology*; D011247:Pregnancy
D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D009842:Oligopeptides; D010446:Peptide Fragments; C526732:SALLRSIPA; C410622:activity-dependent neurotrophic factor; D000431:Ethanol