Reyes E, Ott S
Department of Pharmacology, University of New Mexico, School of Medicine, Albuquerque 87131-5316, USA.
Alcohol Clin Exp Res. 1996 Oct;20(7):1243-51. doi: 10.1111/j.1530-0277.1996.tb01119.x.
The adverse effects of the maternal consumption of alcohol on the fetus have been recognized for centuries. Fetal alcohol syndrome is characterized by pre- and postnatal growth retardation, mental retardation, behavioral deficits, and facial deformities. Despite numerous animal studies, the biochemical mechanism(s) by which alcohol produces teratogenic effects on the developing fetus are not well understood. Several studies have shown that administration of alcohol to adult rats produces a decrease in hepatic levels of glutathione (GSH). In utero administration of alcohol has also been shown to produce a decrease in GSH levels, as well as prenatal growth retardation and intrauterine death. In an effort to determine if GSH may have a vital role in protecting the fetus against the teratogenic effects of alcohol, buthionine (SR)-sulfoximine (BSO) was used to deplete GSH levels in the mother and fetus. Timed pregnant Sprague-Dawley rats were placed on a liquid BioServ diet containing either 0%, 11%, 23%, 29%, 31%, 33%, or 35% ethanol-derived calories, with or without BSO (888 mg/kg/24 hr), starting on day 1 of pregnancy. Another set of mothers were fed lab chow and water as a control group for the liquid diet. The mothers were maintained on the diet until gestation day 21 when they were anesthetized with sodium pentobarbital and the pups delivered by cesarean section. The offspring were counted, weighed, killed, and the brain and liver weighed. The effects of BSO on the alcohol dose-response curves (body weights, brain weights, and litter number) were then determined to ascertain if a depletion in GSH potentiated the effects of alcohol. In utero administration of BSO, aside from the depletion of GSH in the liver and brain in the developing fetus, produced a shift to the left in the alcohol dose-response curve.
母亲饮酒对胎儿的不良影响已被认识了几个世纪。胎儿酒精综合征的特征是产前和产后生长发育迟缓、智力迟钝、行为缺陷和面部畸形。尽管有大量的动物研究，但酒精对发育中的胎儿产生致畸作用的生化机制仍未完全了解。几项研究表明，给成年大鼠喂食酒精会导致肝脏中谷胱甘肽（GSH）水平降低。子宫内给予酒精也已被证明会导致GSH水平降低，以及产前生长发育迟缓和平产死亡。为了确定GSH是否在保护胎儿免受酒精致畸作用方面发挥重要作用，使用丁硫氨酸（SR）-亚砜亚胺（BSO）来耗尽母体和胎儿中的GSH水平。从怀孕第1天开始，将定时怀孕的斯普拉格-道利大鼠置于含有0%、11%、23%、29%、31%、33%或35%乙醇热量的BioServ液体饮食中，添加或不添加BSO（888毫克/千克/24小时）。另一组母亲喂食实验室饲料和水作为液体饮食的对照组。母亲们一直维持这种饮食直到妊娠第21天，此时用戊巴比妥钠麻醉，通过剖宫产分娩幼崽。对幼崽进行计数、称重、处死，然后称量大脑和肝脏的重量。然后确定BSO对酒精剂量反应曲线（体重、脑重和窝仔数）的影响，以确定GSH的耗竭是否会增强酒精的作用。子宫内给予BSO，除了导致发育中胎儿肝脏和大脑中的GSH耗竭外，还使酒精剂量反应曲线向左移动。
