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 METHODS: Following an ethanol acclimation period, female C57Bl/6J mice were withdrawn from the ethanol, bred, and then returned during gestational days (GD) 7 and 8 to a control liquid diet or one containing 4.8% ethanol alone or in combination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.
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 METHODS: Following an ethanol acclimation period, female C57Bl/6J mice were withdrawn from the ethanol, bred, and then returned during gestational days (GD) 7 and 8 to a control liquid diet or one containing 4.8% ethanol alone or in combination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.
Authors: Xiaowei Dou; Carrie E Menkari; Sivananthaperumal Shanmugasundararaj; Keith W Miller; Michael E Charness Journal: J Biol Chem Date: 2011-03-02 Impact factor: 5.157
Authors: Sheryl S Moy; Randal J Nonneman; Geoffrey O Shafer; Viktoriya D Nikolova; Natallia V Riddick; Kara L Agster; Lorinda K Baker; Darin J Knapp Journal: Neurotoxicol Teratol Date: 2012-08-07 Impact factor: 3.763