Biochemical changes in the central nervous system of rats exposed to 1-bromopropane for seven days
Biochemical changes in the central nervous system of rats exposed to 1-bromopropane for seven days
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DOI：
10.1093/toxsci/67.1.114
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发表时间：
2002-05-01
影响因子：
3.8
通讯作者：
Takeuchi, Y
中科院分区：
文献类型：
--
作者：
Wang, HL;Ichihara, G;Takeuchi, Y
1-溴丙烷被广泛用作臭氧消耗溶剂的替代品。在人类和实验动物中描述了该药剂的神经毒性作用。在这里，我们研究了1-溴丙烷的神经毒性作用的潜在机制，通过检查在中枢神经系统的初始生化变化。将4组Wistar雄性大鼠（每组9只）暴露于200、400或800 ppm 1-溴丙烷或仅新鲜空气中，每天8 h，持续7天。实验结束时，从每只大鼠（n = 8）中解剖出大脑、小脑、脑干和脊髓腰膨大用于生化分析。对各组剩余大鼠进行神经系统形态学检查。I-溴丙烷剂量依赖性地降低大脑和小脑中的神经特异性γ-烯醇化酶、总谷胱甘肽和非蛋白巯基。脑和脊髓中肌酸激酶活性呈剂量依赖性降低。组织学检查示薄束核终末前轴突肿胀，周围神经髓鞘变性。我们的γ-烯醇化酶低水平的结果表明，1-溴丙烷可能主要导致大脑和小脑神经元的功能或细胞损失。谷氨酸耗竭或修饰功能蛋白含有巯基作为一个关键网站可能是1-溴丙烷神经毒性的潜在机制。
1-Bromopropane is used widely as an alternative to ozone-depleting solvents. The neurotoxic effects of this agent have been described in humans and experimental animals. Here we investigated the underlying mechanisms of the neurotoxic effects of 1-bromopropane by examining the initial biochemical changes in the central nervous system. Four groups of 9 Wistar male rats each were exposed to 200, 400, or 800 ppm 1-bromopropane or only fresh air, 8 h per day for 7 days. At the end of the experiment, the cerebrum, cerebellum brain stem and lumbar enlargement of the spinal cord were dissected out from each rat (n = 8) for biochemical analyses. Morphological examinations of the nervous system were performed in the remaining rat of each group. I-Bromopropane dose-dependently decreased neurospecific gammaenolase, total glutathione, and nonprotein sulfhydryl groups in the cerebrum and cerebellum. Creatine kinase activity decreased dose-dependently in the brain and spinal cord. Histopathological examination showed swelling of preterminal axons in gracile nucleus and degeneration of myelin in peripheral nerves. Our results of low levels of gamma-enolase suggested that 1-bromopropane might primarily cause functional or cellular loss of neurons in the cerebrum and cerebellum. Glutathione depletion or modification to functional proteins containing a sulfhydryl base as a critical site might be the underlying mechanism of 1-bromopropane neurotoxicity.