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

怀孕的 ICR 小鼠暴露于水中浓度为 0、15 或 50 ppm 或食物中浓度为 125 ppm 的 TBT 氯化物。雄性后代在出生后1周、2周和3周处死。通过 HPLC 测定不同脑区去甲肾上腺素、多巴胺 (DA)、二羟基苯乙酸、高香草酸 (HVA)、血清素 (5-HT) 和 5-羟基吲哚乙酸 (5-HIAA) 的浓度。 125 ppm 组的所有后代在出生后立即死亡。第一周观察到，与对照组相比，TBT 处理的 F1 组体重显着下降。第三周时，与对照组相比，50 ppm F1 组纹状体中的 DA 浓度、15 和 50 ppm F1 组大脑中的 HVA 浓度以及延髓中的 5-HT 浓度均显着增加。三周龄时，神经递质及其代谢物可能是发育神经毒性的有用指标。对于母鼠来说，与对照组相比，125 ppm 组的小脑、延髓、中脑和纹状体中 5-HT 浓度显着降低。与对照组相比，125 ppm 组的母鼠小脑、中脑和纹状体中 5-HIAA 浓度也显着降低。在同一方案中，15 ppm F1 组在 1 周以及 15 ppm 和 50 组中，[^3H]MK-801 与 N-甲基-D-天冬氨酸 (NMDA) 受体的结合水平显着降低。 ppm F1 组在 3 周龄时与相应对照 F1 组相比。

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.