Concurrent dietary administration of D-SAL and ethanol diminishes ethanol's teratogenesis

Alcohol Clin Exp Res. 2007 Dec;31(12):2059-64. doi: 10.1111/j.1530-0277.2007.00524.x. Epub 2007 Oct 19.

Abstract

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Methods: Following an ethanol acclimation period, female C57Bl/6J mice were withdrawn from the ethanol, bred, and then returned during gestational days (GD) 7 and 8 to a control liquid diet or one containing 4.8% ethanol alone or in combination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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Ethanol / antagonists & inhibitors*
  • Ethanol / blood
  • Ethanol / toxicity*
  • Eye Abnormalities / etiology
  • Eye Abnormalities / prevention & control*
  • Female
  • Fetal Alcohol Spectrum Disorders / etiology
  • Fetal Alcohol Spectrum Disorders / prevention & control*
  • Incidence
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / pharmacology*
  • Neuropeptides
  • Oligopeptides
  • Peptide Fragments / pharmacology*
  • Pregnancy

Substances

  • Nerve Tissue Proteins
  • Neuropeptides
  • Oligopeptides
  • Peptide Fragments
  • SALLRSIPA
  • activity-dependent neurotrophic factor
  • Ethanol