Dose-dependent biochemical changes in rat central nervous system after 12-week exposure to 1-bromopropane
Dose-dependent biochemical changes in rat central nervous system after 12-week exposure to 1-bromopropane
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DOI：
10.1016/s0161-813x(02)00195-x
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发表时间：
2003-03-01
期刊：
影响因子：
3.4
通讯作者：
Takeuchi, Y
中科院分区：
文献类型：
--
作者：
Wang, HL;Ichihara, G;Takeuchi, Y
1-溴丙烷在工作场所用作清洁剂或粘合剂溶剂。本文研究了1-溴丙烷对大鼠中枢神经系统(CNS)生化成分的长期影响。4组，每组9只雄性Wistar大鼠，分别暴露于200、400或800ppm的1-溴丙烷或新鲜空气中，每天8小时，每周7天，持续12周。测定大鼠大脑、小脑、脑干和脊髓中神经元特异性伽马烯醇化酶、胶质细胞特异性β-S100蛋白、肌酸激酶(CK)亚基B和M、热休克蛋白Hsp27(酶免疫法)、CK酶活性以及谷胱甘肽(GSH)、氧化谷胱甘肽(GSSG)和硫代(SH)碱的含量。大脑中的伽马烯醇化酶呈剂量依赖性下降，表现为湿重下降，达到或超过400ppm，但任何大脑区域或脊髓中的β-S100蛋白都没有变化。HSP27在小脑、脑干和脊髓中表达降低。各脑区蛋白结合SH碱、非蛋白SH碱和总谷胱甘肽含量均下降。CK活性在200ppm或以上呈剂量依赖性下降，CK活性与CK-B浓度的比值在所有地区均呈下降趋势。大脑中伽马烯醇化酶的减少表明，随着大脑湿重的减少，神经元中的生化变化也参与其中。1-溴丙烷的神经毒性机制可能是谷胱甘肽的耗竭和以SH碱为关键部位的蛋白质的改变。大脑中的生化变化表明，长期接触1-溴丙烷对中枢神经系统有影响。(C)2002 Elsevier Science Inc.保留所有权利。
1-Bromopropane is used as a cleaning agent or adhesive solvent in the workplace. The present study investigated the long-tern effects of exposure to 1-bromopropane on biochemical components in the central nervous system (CNS) of rats. Four groups, each of nine male Wistar rats, were exposed to 200, 400, or 800 ppm 1-bromopropane or fresh air only, 8 h per day, 7 days a week for 12 weeks. We measured the levels of neuron-specific gamma-enolase, glia-specific beta-S100 protein, creatine kinase (CK) subunits B and M, heat shock protein Hsp27 (by enzyme immunoassay), enzymatic activity of CK and levels of glutathione (GSH), oxidized glutathione (GSSG) and sulfhydrul (SH) base in the cerebrum, cerebellum, brainstem and spinal cord. gamma-Enolase decreased dose-dependently in the cerebrum, which showed a decrease in wet weight, at 400 ppm or over, but no change was noted in beta-S100 protein in any brain region or spinal cord. Hsp27 decreased in the cerebellum, brainstem and spinal cord. Protein-bound SH base, non-protein SH base and total glutathione decreased in every brain region. CK activity decreased dose-dependently at 200 ppm or over, and the ratio of CK activity to CK-B concentration tended to decrease in all regions. The decrease in gamma-enolase in the cerebrum suggests the involvement of biochemical changes in neurons with decrease in the wet weight of the cerebrum. Glutathione depletion and changes in proteins containing SH base as a critical site might be the underlying neurotoxic mechanism of 1-bromopropane. The biochemical changes in the cerebrum indicate that long-term exposure to 1-bromopropane has effects on the CNS. (C) 2002 Elsevier Science Inc. All rights reserved.