Institut National de Recherche et de Sécurité, Rue du Morvan, CS 60027, F-54519 Vandœuvre Cedex, France.
Institut National de Recherche et de Sécurité, Rue du Morvan, CS 60027, F-54519 Vandœuvre Cedex, France; Departament de Ciències Fisiològiques and Institute of Neurosciences, Universitat de Barcelona, 08907 L'Hospitalet de Llobregat, Catalonia, Spain.
Neurotoxicology. 2018 Jul;67:270-278. doi: 10.1016/j.neuro.2018.06.010. Epub 2018 Jun 19.
Chronic occupational exposure to carbon disulfide (CS2) has debilitating motor and sensory effects in humans, which can increase the risk of falls. Although no mention of vestibulotoxic effects is contained in the literature, epidemiological and experimental data suggest that CS2 could cause low-frequency hearing loss when associated with noise exposure. Low-frequency noise might also perturb the peripheral balance receptor through an as-yet unclear mechanism. Here, we studied how exposure to a low-frequency noise combined with 250-ppm CS2 affected balance in rats. Vestibular function was tested based on post-rotary nystagmus recorded by a video-oculography system. These measurements were completed by behavioral tests and analysis of the cerebellum to measure expression levels for gene expression associated with neurotoxicity. Assays were performed prior to and following a 4-week exposure, and again after a 4-week recovery period. Functional measurements were completed by histological analyses of the peripheral organs.Nystagmus was unaltered by exposure to noise alone, while CS2 alone caused a moderate 19% decrease of the saccade number. In contrast, coexposure to 250-ppm CS2 and low-frequency noise decreased both saccade number and duration by 33% and 34%, respectively. After four weeks, recovery was only partial but measures were not significantly different from pre-exposure values. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis of cerebellar tissue revealed a slight but significant modification in expression levels for two genes linked to neurotoxicity in CS2-exposed animals. However, neither histopathological changes to the peripheral receptor nor behavioral differences were observed. Based on all these results, we propose that the effects of CS2 were due to reversible neurochemical disturbance of the efferent pathways managing post-rotatory nystagmus. Because the nervous structures involving the vestibular function appear particularly sensitive to CS2, post-rotary nystagmus could be used as an early, non-invasive measurement to diagnose CS2 intoxication as part of an occupational conservation program.
慢性职业性接触二硫化碳（CS2）会对人体的运动和感觉功能造成损害，增加跌倒的风险。尽管文献中没有提到前庭毒性作用，但流行病学和实验数据表明，CS2 与噪声接触时可能导致低频听力损失。低频噪声也可能通过尚未明确的机制扰乱外周平衡感受器。在这里，我们研究了低频噪声与 250ppm CS2 联合暴露如何影响大鼠的平衡。前庭功能通过视频眼震图系统记录的旋转后眼球震颤来测试。这些测量是通过行为测试和小脑分析来完成的，以测量与神经毒性相关的基因表达水平。在 4 周暴露前、暴露后和 4 周恢复期进行了检测。功能测量通过外周器官的组织学分析完成。单独暴露于噪声不会引起眼球震颤的改变，而单独暴露于 CS2 会导致眼球跳动次数中度减少 19%。相比之下，同时暴露于 250ppm CS2 和低频噪声会分别使眼球跳动次数和持续时间减少 33%和 34%。四周后，恢复仅部分完成，但测量值与暴露前值无显著差异。小脑组织的实时定量聚合酶链反应（RT-qPCR）分析显示，CS2 暴露动物与神经毒性相关的两个基因的表达水平略有但显著改变。然而，没有观察到外周感受器的组织病理学变化或行为差异。基于所有这些结果，我们提出 CS2 的作用是由于管理旋转后眼球震颤的传出途径的神经化学紊乱是可逆的。由于涉及前庭功能的神经结构对 CS2 特别敏感，因此旋转后眼球震颤可以作为一种早期、非侵入性的测量方法，用于诊断 CS2 中毒，作为职业保护计划的一部分。
