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亚砷酸钠在器官形成中期处理的孕鼠的胎儿脑以及血浆、肝脏、脑和肾脏的游离脂肪酸谱

Free fatty acids profile of the fetal brain and the plasma, liver, brain and kidneys of pregnant rats treated with sodium arsenite at mid-organogenesis.

作者信息

Ross Ivan A, Boyle Thomas, Johnson Widmark D, Sprando Robert L, O'Donnell Michael W, Ruggles Dennis, Kim Chung S

机构信息

Center for Food Safety and Applied Nutrition, Division of Toxicology, Office of Applied Research and Safety Assessment, Laurel, MD, USA.

出版信息

Toxicol Ind Health. 2010 Nov;26(10):657-66. doi: 10.1177/0748233710375952. Epub 2010 Jul 14.

Abstract

Free fatty acids (FFAs) are known to be markers of cellular membrane degradation through lipid peroxidation and are substrates for the production of reactive oxygen species (ROS). Oxidative stress, due to overproduction of ROS, may facilitate cellular insult by various toxicants. The ability of the rat conceptus to respond to toxic stress may be critical for normal development. In this study, the effects of the environmental toxicant sodium arsenite (NaAsO₂) on FFAs were investigated after administering a single oral dose, in water and in a lipid medium, to pregnant rats on gestational day (GD) 10, a time point at mid-organogenesis. NaAsO₂ was administered in deionized water (AsH₂O) or in half and half dairy cream (AsHH) at a dose of 41 mg sodium arsenite (NaAsO₂)/kg body weight. Control animals were treated with either dairy cream (HH) or deionized water (H₂O). The animals were sacrificed on GD 20. The fetal brain and the maternal liver, brain, plasma and kidneys were harvested. The FFAs were extracted and analyzed by gas chromatography. In the liver, there was an increase of myristic acid (1200%), myristoleic acid (174%), palmitic acid (47%), elaidic acid (456%), oleic acid (165%) and docosahexaenoic acid (224%) in the AsH₂O group as compared to the AsHH group. Oleic acid and arachidonic acid were increased by 192% and 900%, respectively, in the AsH₂O group as compared to the H₂O group, and myristic acid was decreased by 90% in the AsHH group as compared to the HH group. In the maternal brain, myristoleic acid was decreased by 91% in the AsH₂O group as compared to the H₂O group, and DHA increased by 148% in the AsHH group as compared to the HH group. In the fetal brain, myristic and stearic acids were decreased by 87% and 89%, respectively, in the AsH₂O group as compared to the AsHH group. Myristic, stearic and arachidonic acids were increased by 411%, 265%, and 144%, respectively, in the AsHH group as compared to the HH group. There was no effect on the fatty acids concentrations in the kidney or plasma as compared to controls. This study shows that NaAsO₂ produced a differential effect on the fatty acid profiles in rats. Further investigation is needed to elucidate the role of fatty acids in differential signaling and regulation by either the palmitoylation or myristoylation process of cellular functions in these target organs.

摘要

游离脂肪酸(FFAs)是细胞膜通过脂质过氧化作用发生降解的标志物,也是活性氧(ROS)生成的底物。由于ROS产生过多导致的氧化应激,可能会促进各种毒物对细胞的损害。大鼠胚胎对毒性应激的反应能力可能对其正常发育至关重要。在本研究中,于妊娠第10天(GD 10,器官形成中期的一个时间点)给怀孕大鼠经口单次给予环境毒物亚砷酸钠(NaAsO₂),分别溶于水和脂质介质中,研究其对游离脂肪酸的影响。以41 mg亚砷酸钠(NaAsO₂)/kg体重的剂量将NaAsO₂溶于去离子水(AsH₂O)或半乳脂奶油(AsHH)中。对照动物分别用乳脂奶油(HH)或去离子水(H₂O)处理。在GD 20处死动物。采集胎儿脑以及母体的肝脏、脑、血浆和肾脏。提取游离脂肪酸并通过气相色谱法进行分析。在肝脏中,与AsHH组相比,AsH₂O组的肉豆蔻酸(增加1200%)、肉豆蔻油酸(增加174%)、棕榈酸(增加47%)、反油酸(增加456%)、油酸(增加165%)和二十二碳六烯酸(增加224%)含量升高。与H₂O组相比,AsH₂O组的油酸和花生四烯酸分别增加192%和900%;与HH组相比,AsHH组的肉豆蔻酸含量降低90%。在母体脑中,与H₂O组相比,AsH₂O组的肉豆蔻油酸含量降低91%;与HH组相比,AsHH组的DHA含量增加148%。在胎儿脑中,与AsHH组相比,AsH₂O组的肉豆蔻酸和硬脂酸含量分别降低87%和89%。与HH组相比,AsHH组的肉豆蔻酸、硬脂酸和花生四烯酸含量分别增加411%、265%和144%。与对照组相比,对肾脏或血浆中的脂肪酸浓度没有影响。本研究表明,NaAsO₂对大鼠的脂肪酸谱产生了差异性影响。需要进一步研究以阐明脂肪酸在这些靶器官细胞功能的棕榈酰化或豆蔻酰化过程中差异性信号传导和调节中的作用。

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