The experimental study for the evaluation of the developmental neurotoxicity of tributyltin compounds

三丁基锡化合物发育神经毒性评价的实验研究

基本信息

批准号：
15590516
负责人：
TSUNODA Masashi
金额：
$ 2.3万
依托单位：
Kitasato University (2004-2005)Fukushima Medical University (2003)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

Pregnant ICR mice were exposed to TBT chloride at concentrations of 0, 15, or 50 ppm in water or 125 ppm in food. Male offspring were sacrificed at 1, 2 and 3 weeks after birth. The concentrations of norepinephrine, dopamine (DA), dihydoxyphenylacetic acid, homovanillic acid (HVA), serotonin (5-HT), and 5-hydroxyindolacetic acid (5-HIAA) were determined in different brain regions by HPLC. All offspring from the 125 ppm group died immediately after birth. A significant decrease in the body weight of the TBT-treated F1 groups compared to the control group was observed at the first week. Significant increases compared to the controls were observed for the DA concentration in the striatum of the 50 ppm F1 group, and for the HVA concentration in the cerebrum and the 5-HT concentration in the medulla oblongata of the 15 and 50 ppm F1 groups at the third week. At three weeks of age, the neurotransmitters and their metabolites may be useful indexes for developmental neurotoxicity. For the dams, a significant decrease in the 5-HT concentration was observed in the cerebellum, medulla, midbrain and striatum of the 125 ppm group compared to the control group. A significant decrease in the 5-HIAA concentration was also observed in the cerebellum, midbrain and striatum of the dams in the 125 ppm group compared to the control.In the same protocol, the [^3H]MK-801 binding level to N-methyl-D-aspartate (NMDA) receptors siginificantly decreased in the 15 ppm F1 group at 1 week and in the 15 ppm and 50 ppm F1 groups at 3 weeks of age, compared with that in the corresponding control F1 group.

在水中以0、15或50 ppm的浓度或食物中的125 ppm暴露于TBT氯化物中。在出生后1、2和3周处以雄性后代牺牲。 HPLC在不同的大脑区域确定去甲肾上腺素，多巴胺（DA），二羟基苯基乙酸，同甲基酸（HVA），5-羟基甲酸（5-HT）和5-羟基乙酸（5-HIAA）的浓度。 125 ppm组的所有后代在出生后立即死亡。与对照组相比，通过TBT处理的F1组的体重显着减少。与对照组相比，观察到50 ppm F1组的纹状体的DA浓度以及大脑中的HVA浓度和HVA浓度的显着增加，在第三周的15和50 ppm f1组的髓质浓度中的HVA浓度和5-HT浓度。在三周大时，神经递质及其代谢物可能是发育神经毒性的有用指数。对于大坝，与对照组相比，在125 ppm组的小脑，髓质，中脑和纹状体中观察到5-HT浓度显着降低。与对照组相比，在125 ppm组的小脑，中脑和大坝的小脑，中脑和纹状体中也观察到5-HIAA浓度的显着降低。在同一方案中，[^3H] MK-801与N-甲基-D-甲酸盐（NMDA）受体（NMDA）受体的结合水平[^3H] MK-801结合水平在15 ppm和50 ppm and in 50 ppm and in 50 ppm and。与相应的对照F1组相比，3周龄的F1组。