Effects of in utero administration of alcohol on glutathione levels in brain and liver.

Effects of in utero administration of alcohol on glutathione levels in brain and liver.
复制标题

子宫内饮酒对大脑和肝脏谷胱甘肽水平的影响。

DOI:
10.1111/j.1530-0277.1993.tb00857.x
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发表时间:
1993
期刊:
Alcoholism, clinical and experimental research
影响因子:
--
通讯作者:
Robinson,B
Robinson,B
中科院分区:
--
文献类型:
--
作者:
Reyes,E;Ott,S;Robinson,B

文献摘要

被引文献

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我们实验室先前的研究表明,子宫内给予酒精会延迟γ-谷氨酰转肽酶(γ-GTP)活性的个体发育。γ-GTP通过γ-谷氨酰循环负责谷胱甘肽(GSH)的降解和再循环。在这项研究中,我们研究了宫内注射酒精对胎龄21天(g21)大鼠GSH水平的影响。从妊娠第1天开始,对妊娠大鼠喂食含35%乙醇衍生卡路里(35%EDC)的流质饲料或配对喂养(PF)饲料或实验室食物(LC)饲料,并维持其各自的饲料直至妊娠第21天。在妊娠第21天,通过剖腹产分娩幼仔,取出大脑和肝脏,并准备用于GSH、γ-GTP或γ-谷氨酰半胱氨酸合成酶(γ-GCSyn)分析。发现35% EDC处理母体的后代的脑和肝脏中GSH水平显著低于PF和LC对照。35%EDC组脑和肝中γ-GTP活性高于PF组。与LC组相比,35% EDC和PF组肝脏中参与GSH合成限速步骤的酶γ-GCSyn未受影响,但发现脑中γ-GCSyn降低。GSH参与许多细胞反应,似乎可以保护细胞免受损害。在发育过程中,酒精对GSH的消耗可能使发育中的胎儿更容易受到酒精或其代谢产生的自由基的毒性作用。
Previous studies in our laboratory have shown that the ontogenic development of γ‐glutamyltranspeptidase (γ‐GTP) activity is delayed by the in utero administration of alcohol. γ‐GTP is responsible for the degradation and recycling of glutathione (GSH) via the γ‐glutamyl cycle. In this study, we examined the effects of the in utero administration of alcohol on GSH levels in gestational age 21‐day‐old (g21) rats. Pregnant rats were placed on a liquid diet containing either 35% ethanol‐derived calories (35% EDC) or a pair‐fed (PF) diet or a lab chow (LC) diet starting on day 1 of gestation and maintained on their respective diets until gestational day 21. On gestational day 21, the pups were delivered by Cesarean section and brains and livers removed and prepared for analysis of GSH, γ‐GTP, or γ‐glutamylcysteine synthetase (γ‐GCSyn). GSH levels in brain and liver were found to be significantly lower in the offspring of the 35% EDC‐treated mothers than from the PF and LC controls. γ‐GTP activity was higher in brain and liver of the 35% EDC group than the PF group. γ‐GCSyn, the enzyme involved in the rate‐limiting step of GSH synthesis, was not affected in liver, but was found to be decreased in brain of the 35% EDC and PF groups when compared with the LC group. GSH is involved in many cellular reactions that appear to protect the cell from damage. The depletion of GSH by alcohol during development may make the developing fetus more susceptible to the toxic effects of alcohol or the free radicals generated by its metabolism.