Hungund B L, Gokhale V S
New York State Psychiatric Institute, New York 10032.
Biochem Pharmacol. 1994 Nov 29;48(11):2103-8. doi: 10.1016/0006-2952(94)90511-8.
The biochemical mechanism of alcohol teratogenicity is not known. We have demonstrated that alcohol administration to pregnant rats during gestation days (GD) 6 and 7 and/or 13 and 14 leads to significant accumulation of ethyl esters of long chain fatty acids (FAEEs) in both maternal and fetal organs. This observation extends the report of Bearer et al. (Pediat Res 31: 492-495, 1992) who detected the presence of metabolites in maternal and fetal organs of pregnant C57B1/6J mice exposed to alcohol on GD 7 and/or GD 14. The ethyl esters of arachidonic, linoleic, oleic, stearic and palmitic acids were major metabolites detected in both maternal and fetal organs. It was also demonstrated that detectable levels of FAEEs remain 14 days (GD 20) after initial exposure to alcohol on GD 7. Ganglioside GM1 treatment 1 and 24 hr prior to alcohol exposure on both GD 7 and/or GD 14 reduced the accumulation of FAEEs. A similar regimen was shown to prevent development of tolerance to alcohol in the adult pups exposed to alcohol in utero in our previous studies. Thus, the ganglioside GM1 may have therapeutic value in reducing neurobehavioral effects of alcohol exposure in utero.
酒精致畸的生化机制尚不清楚。我们已经证明,在妊娠第6和7天及/或13和14天给怀孕大鼠施用酒精会导致母体和胎儿器官中长链脂肪酸乙酯(FAEEs)显著积累。这一观察结果扩展了Bearer等人的报告(《儿科研究》31: 492 - 495, 1992),他们在妊娠第7天和/或第14天暴露于酒精的怀孕C57B1/6J小鼠的母体和胎儿器官中检测到了代谢产物的存在。花生四烯酸、亚油酸、油酸、硬脂酸和棕榈酸的乙酯是在母体和胎儿器官中检测到的主要代谢产物。还证明了在第7天首次暴露于酒精后,可检测到的FAEEs水平在14天(妊娠第20天)内持续存在。在第7天和/或第14天酒精暴露前1小时和24小时给予神经节苷脂GM1可减少FAEEs的积累。在我们之前的研究中,类似的方案被证明可以预防子宫内暴露于酒精的成年幼崽对酒精产生耐受性。因此,神经节苷脂GM1在减轻子宫内酒精暴露的神经行为影响方面可能具有治疗价值。