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首页> 外文学位 >Neurotoxicity and neurobehavioral effects of manganese phosphate/sulfate mixture in male Sprague-Dawley rats following subchronic inhalation exposure .
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Neurotoxicity and neurobehavioral effects of manganese phosphate/sulfate mixture in male Sprague-Dawley rats following subchronic inhalation exposure .

机译：亚慢性吸入暴露对雄性Sprague-Dawley大鼠磷酸锰/硫酸锰混合物的神经毒性和神经行为的影响。

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摘要

Methylcyclopentadienyl manganese tricarbonyl (NWT) is an organic manganese (Mn) compound added to unleaded gasoline in Canada. The primary combustion products of MMT are Mn phosphate, Mn sulfate, and Mn phosphate/sulfate mixture. Concerns have been raised that the combustion products of MMT could be neurotoxic, even at low levels of exposure. The objective of this study is to assess and compare tissue concentration following subchronic inhalation exposure to a mixture of Mn phosphate/sulfate particles in rats exposed at low, intermediate and high levels. This research aims also to assess the neuropathology and neurobehavioral effects associated with exposure to the mixture.; A control group and three groups of 30 male Sprague-Dawley rats were exposed in inhalation chambers for a period of 13 weeks, 5 days per week, 6 hours a day. Exposure concentrations were 3000, 300, and 30 mug/m 3. The neuropathology aspect of this study was to count neuronal cells in globus pallidus, caudate putamen, and frontal cortex. Also the neurobehavioral change was measured by assessing locomotor activity and tremor among groups. In each group, half of the rats were implanted with chronic EMG electrodes in the gastrocnemius muscle of the hind lamb for the purpose of measuring tremor. Tremor assessment was conducted one hour after the last exposure by recording muscle EMG activity for approximately 5 minutes with implanted EMG electrode rats while resting in the cage, walking on the floor, and standing on a vertical 39 cm metal screen grid.; At the end, locomotor activity test was conducted for 36 hours using a computerized autotrack system. Rats were then sacrificed by exsanguinations, and Mn concentration in different tissues (liver, lung, testis, and kidney), blood and brain (caudate putamen, globus pallidus, olfactory bulb, frontal cortex, and cerebellum) were determined by neutron activation analysis. Increased manganese concentrations were observed in blood, kidney, lung, testis, and in all brain sections in the highest exposure group. Mn in the lung and in the olfactory bulb was dose-dependent. Our data indicate that the olfactory bulb accumulated more Mn than other brain regions following inhalation exposure. Biochemical profiles also revealed some significant differences in certain parameters, specifically alkaline phosphatase, urea, and chlorate.; Locomotor activity was significantly increased at 30 and 3000 mug/m 3. The neuronal cell loss was significantly different in all three areas of interest for rats exposed to the highest level of exposure (3000 mug/m 3). The result does not show any sign of tremor. In conclusion, exposure to Mn phosphate/sulfate mixture leads to onset the neuropathological changes in particular area of the brain and causes some neurobehavioral differences among the rats.
机译：甲基环戊二烯基三羰基锰（NWT）是加拿大的一种添加到无铅汽油中的有机锰（Mn）化合物。 MMT的主要燃烧产物是磷酸锰，硫酸锰和磷酸锰/硫酸盐混合物。有人担心即使在低暴露水平下，MMT的燃烧产物也可能具有神经毒性。这项研究的目的是评估和比较亚慢性吸入暴露于低，中和高水平大鼠的亚磷酸锰/硫酸锰颗粒混合物的组织浓度。该研究的目的还在于评估与暴露于混合物中相关的神经病理学和神经行为作用。对照组和三组30只雄性Sprague-Dawley大鼠在吸入室中暴露，暴露时间为13周，每周5天，每天6小时。暴露浓度分别为3000、300和30 mug / m3。该研究的神经病理学方面是对苍白球，尾状壳和额叶皮层中的神经元细胞进行计数。还通过评估各组之间的运动活动和震颤来测量神经行为的变化。在每组中，一半的大鼠在后羊的腓肠肌中植入了慢性EMG电极，以测量震颤。在最后一次暴露后一小时，通过植入EMG电极大鼠记录肌肉EMG活性约5分钟，同时躺在笼子里，在地板上行走，并站在垂直的39厘米金属筛网上，进行震颤评估。最后，使用计算机自动跟踪系统进行了36小时的运动活动测试。然后通过放血处死大鼠，并通过中子活化分析确定不同组织（肝，肺，睾丸和肾脏），血液和大脑（尾状壳壳核，苍白球，嗅球，额叶皮层和小脑）中的锰浓度。在最高暴露水平的人群中，血液，肾脏，肺，睾丸和所有脑部的锰含量均升高。肺和嗅球中的锰是剂量依赖性的。我们的数据表明，吸入暴露后，嗅球比其他大脑区域积累更多的Mn。生化特征还显示某些参数存在一些显着差异，特别是碱性磷酸酶，尿素和氯酸盐。在暴露于最高暴露水平（3000 mug / m 3）的大鼠中，自发活动在30和3000 mug / m 3时显着增加。在所有三个感兴趣的区域，神经元细胞损失均显着不同。结果未显示任何震颤迹象。总之，暴露于磷酸锰/硫酸锰混合物会导致大脑特定区域发生神经病理变化，并在大鼠之间引起某些神经行为差异。

著录项

  • 作者

    Salehi, Fariba.;

  • 作者单位

    Universite de Montreal (Canada).;

  • 授予单位 Universite de Montreal (Canada).;
  • 学科 Health Sciences Toxicology.
  • 学位 Ph.D.
  • 年度 2005
  • 页码 245 p.
  • 总页数 245
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 毒物学（毒理学）;
  • 关键词

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