IN-UTERO ETHANOL EXPOSURE ELICITS OXIDATIVE STRESS IN THE RAT FETUS
IN-UTERO ETHANOL EXPOSURE ELICITS OXIDATIVE STRESS IN THE RAT FETUS
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DOI：
10.1111/j.1530-0277.1995.tb01572.x
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发表时间：
1995-06-01
影响因子：
3.2
通讯作者：
SCHENKER, S
中科院分区：
文献类型：
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作者：
HENDERSON, GI;DEVI, BG;SCHENKER, S
我们实验室先前的研究表明，暴露于培养的胎鼠肝细胞的乙醇（E）阻断表皮生长因子依赖性复制，这是由细胞膜损伤，线粒体功能障碍，膜脂质过氧化（LP），和活性氧的产生增加。这些措施的E-介导的氧化应激（OS）的治疗与抗氧化剂减轻，细胞复制可以正常化，通过维持细胞谷胱甘肽（GSH）池。我们现在已经将这些研究扩展到体内模型。在妊娠第17天和第18天，每隔12小时对大鼠给予E（4 g/kg，po），并在第19天（E末次给药后1小时）处死（共5次给药）。胎儿和母亲的大脑和肝脏的OS的迹象进行了分析。2天的子宫内E暴露增加膜LP在胎儿的大脑中，证明了增加的丙二醛（MDA）水平从1.76 +/- 0.12 SE 00 +/-0.08（p < 0.05），并且共辄二烯从0.230 +/-0.006se（OD 233脂质）至0.282 +/-0.006（p < 0.05）。在胎肝中，MDA水平从2.39 +/- 0.08 SE（nMol/mg蛋白质）增加到2.87 +/- 0.08（p < 0.05），而二烯仅在自由采食对照组与E和成对饲喂对照组之间存在显著差异（p < 0.05）。E使胎儿脑中GSH水平降低19%，从19.88 +/- 0.72降至16.13 +/- 1.06（nMol/mg蛋白）（p < 0.05）。在胎肝中观察到GSH降低10%（p < 0.05）。母体脑中GSH从47.29 ± 3.38下降到26.60 ± 2.29（p < 0.05），下降了44%。在母体器官中未观察到这些OS指标的其他E相关增加。E没有降低胎儿和母体脑或胎儿肝脏中的α-生育酚水平（p < 0.05），而母体肝脏α-生育酚含量通过E处理降低了31%（p < 0.05）。结论：母体摄入E可诱导胎儿组织中OS，这可能有助于E的胎儿毒性作用。
Prior studies in our laboratory have shown that exposure of cultured fetal rat hepatocytes to ethanol (E) blocks epidermal growth factor-dependent replication and that this is paralleled by cell membrane damage, mitochondrial dysfunction, membrane lipid peroxidation (LP), and enhanced generation of reactive oxygen species. These measures of E-mediated oxidative stress (OS) were mitigated by treatment with antioxidants, and cell replication could be normalized by maintaining cell glutathione (GSH) pools. We have now extended these studies to an in vivo model. Rats were administered E (4 g/kg, po) at 12-hr intervals on days 17 and 18 of gestation and killed on day 19, 1 hr following a final dose of E (a total of 5 doses). Fetal and maternal brain and liver were assayed for signs of OS. The 2-day in utero E exposure increased membrane LP in fetal brain as evidenced by increased malondialdehyde (MDA) levels from 1.76 +/- 0.12 SE (nMol/mg protein) to 2.00 +/- 0.08 (p < 0.05) and conjugated dienes from 0.230 +/- 0.006 se (OD233 lipid) to 0.282 +/- 0.006 (p < 0.05). In fetal liver, MDA levels increased from 2.39 +/- 0.08 SE (nMol/mg protein) to 2.87 +/- 0.08 (p < 0.05), whereas dienes differed significantly only between ad libitum controls and the E and pair-fed control groups (p < 0.05). E decreased GSH levels in fetal brain by 19%, from 19.88 +/- 0.72 to 16.13 +/- 1.06 (nMol/mg protein) (p < 0.05). A 10% decrease in GSH was seen in fetal liver(p < 0.05). GSH in maternal brain was decreased by 44% from 47.29 +/- 3.38 to 26.60 +/- 2.29 (p < 0.05). Other E-related increases in these OS measures were not observed in maternal organs. E did not decrease alpha-tocopherol levels in fetal and maternal brain or in fetal liver (p < 0.05), whereas maternal liver alpha-tocopherol content was reduced by 31% (p < 0.05) by E treatment. It is concluded that maternal E consumption can induce an OS in fetal tissues that may contribute to the fetotoxic effects of E.