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孕期和哺乳期接触低剂量邻苯二甲酸二己酯会导致大鼠海马行为缺陷,并加剧氧化应激。

Prenatal and breastfeeding exposure to low dose of diethylhexyl phthalate induces behavioral deficits and exacerbates oxidative stress in rat hippocampus.

机构信息

Student Research Committee, Babol University of Medical Sciences, Babol, Iran; Department of Pharmacology and Toxicology, School of Medicine, Babol University of Medical Sciences, Babol, Iran.

Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran; Department of Pharmacology and Toxicology, School of Medicine, Babol University of Medical Sciences, Babol, Iran.

出版信息

Food Chem Toxicol. 2021 Aug;154:112322. doi: 10.1016/j.fct.2021.112322. Epub 2021 Jun 7.

DOI:10.1016/j.fct.2021.112322
PMID:34111487
Abstract

Diethylhexyl phthalate (DEHP) is one of the most important derivatives of phthalate that has devastating effects on nervous system function. In this study, the effects of exposure with low doses of DEHP during pregnancy and lactation periods have been evaluated in rat's puppies. DEHP at doses 5, 40, 400 μg/kg/day and 300 mg/kg/day was given to mothers by gavage during pregnancy and lactation. The spatial and working memories were evaluated by Morris water maze test and Y maze, respectively. Oxidative stress levels were measured by biochemical tests. Histopathology of hippocampal tissue was assessed using hematoxylin and eosin, Nissl staining, and immunohistofluorescence in 60-days-old puppies. Behavioral data showed that low doses of DEHP decreased the working and spatial memories of male rats. Increased oxidative stress and decreased antioxidant activity were also observed in the hippocampus of rats which received the low doses of DEHP. However, neuronal damage, inflammation, and astrocyte activation were not significantly increased in the hippocampus of rats. Overall, exposure of mothers to low doses of DEHP during pregnancy and lactation cause behavioral deficits, especially in male newborn. The destructive effects of low doses of DEHP might be mediated through increased levels of oxidative stress in the brain.

摘要

邻苯二甲酸二(2-乙基)己酯(DEHP)是邻苯二甲酸酯的最重要衍生物之一,对神经系统功能具有破坏性影响。在这项研究中,评估了在怀孕和哺乳期暴露于低剂量 DEHP 对大鼠幼崽的影响。通过灌胃在怀孕期间和哺乳期给母亲施用 DEHP,剂量为 5、40、400μg/kg/天和 300mg/kg/天。通过 Morris 水迷宫测试和 Y 迷宫分别评估空间和工作记忆。通过生化测试测量氧化应激水平。在 60 天大的幼崽中使用苏木精和伊红、尼氏染色和免疫荧光染色评估海马组织的组织病理学。行为数据表明,低剂量的 DEHP 降低了雄性大鼠的工作和空间记忆。还观察到接受低剂量 DEHP 的大鼠海马中的氧化应激增加和抗氧化活性降低。然而,在大鼠海马中,神经元损伤、炎症和星形胶质细胞激活没有明显增加。总体而言,母亲在怀孕和哺乳期暴露于低剂量 DEHP 会导致行为缺陷,尤其是在雄性新生儿中。低剂量 DEHP 的破坏作用可能通过大脑中氧化应激水平的增加来介导。

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