Occupational exposure to manganese and noise potentiate hearing loss

职业接触锰和噪音会加剧听力损失

• 批准号: 8270945
• 负责人: JEROME Allan ROTH
• 金额: $ 48.23万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8270945
• 关键词: Occupational; exposure; manganese; noise; potentiate

DESCRIPTION (provided by applicant): Manganese (Mn) toxicity is characterized by a collection of neurological symptoms similar to the extrapyramidal dysfunction associated with Parkinson's disease. In the US and other developed countries, manganism is primarily an occupational disorder most often seen in the welding profession because welding rods contain relatively high quantities of Mn. Gases that are given off by the extreme heat generated from the welding guns vaporize the Mn in the rods which is either taken up into the lungs and subsequently transported into the circulation or directly transported into the CNS via retrograde transport through the olfactory neurons impinging on the nasal cavity. Epidemiological studies and case reports indicate that prolonged exposure to high atmospheric levels of Mn can cause hearing impairment. In support of these clinical reports is a recently published study from our laboratory demonstrating for the first time that ¿M levels of Mn initially damages spiral ganglion neurons and then the sensory hair cells in organotypic cultures of rat inner ear. Preliminary in vivo studies indicate that Mn can impair hearing and damage cochlear neurons in rats. This is consistent with another recent report, demonstrating that welding fumes induce hearing impairment in rabbits and that the hearing deficits are exacerbated by exposure to noise. Since Mn has been reported to accumulate in the inner ear (cochlea) following acute treatment, we hypothesize that it has the potential to damage the sensory hair cells that convert sound into neural activity or spiral ganglion neurons (SGN) that transmit acoustic information from the hair cells to the brain via the auditory nerve. Moreover, we hypothesize that Mn-induced hearing loss observed in welders is exacerbated by the high levels of noise present in the occupational working environment. To test these hypotheses, we propose perform in vivo studies to establish a dose-time response relationship for the ototoxic effects of Mn administered orally to rats. We will test the hypothesis that concurrent exposure to high level of continuous noise will exacerbate hearing impairment and cochlear pathology induced by Mn. We will also correlate the extent of hearing impairment with Mn concentrations in the inner ear as a function of time and dose and noise exposure. To accomplish this, we will determine the degree of hearing impairment that develops from various doses of Mn alone, noise alone and Mn plus noise. We will also compare and evaluate histopathological damage produced by Mn, noise and the combination of Mn plus noise; this will be accomplished by assessing degeneration of the stria vascularis, hair cells and SGN death. We will correlate the degree of hearing impairment and cochlear histopathologies for each treatment paradigm with the Mn concentration in the cochlea. PUBLIC HEALTH RELEVANCE: Several reports in the literature have described hearing deficits both in welders who are normally exposed to chronic high levels of Mn and in individuals exposed simultaneous to noise and Mn. Our recent published findings demonstrate that exposure to Mn can cause degeneration of cells within the inner ear and further reveal that these lesions can provoke auditory impairment in rats treated with the divalent metal. The relevance of the studies proposed will enable us to understand the mechanism for Mn-induced auditory loss with the intent to find new treatments to prevent this from occurring.

描述（由申请方提供）：锰（Mn）毒性的特征是一系列神经系统症状，类似于帕金森病相关的锥体外系功能障碍。在美国和其他发达国家，锰中毒主要是一种职业病，最常见于焊接行业，因为焊条含有相对较高的锰量。由焊枪产生的极热释放的气体使杆中的Mn蒸发，其被吸入肺中并随后被输送到循环中，或经由逆行输送通过撞击鼻腔的嗅觉神经元直接输送到CNS中。流行病学研究和病例报告表明，长期暴露于大气中高浓度的锰可导致听力损伤。为了支持这些临床报告，我们实验室最近发表的一项研究首次证明，在大鼠内耳器官型培养物中，<$M水平的Mn首先损害螺旋神经节神经元，然后损害感觉毛细胞。初步的体内研究表明，锰可以损害听力和损害耳蜗神经元在大鼠。这与最近的另一份报告一致，该报告表明焊接烟雾会导致兔子听力受损，并且听力缺陷会因暴露于噪音而加剧。由于已报告Mn在急性治疗后在内耳（耳蜗）中蓄积，因此我们假设它有可能损伤将声音转化为神经活动的感觉毛细胞或通过听觉神经将声音信息从毛细胞传递到大脑的螺旋神经节神经元（SGN）。此外，我们假设，锰引起的听力损失的焊工是加剧了高水平的噪音存在于职业工作环境中。为了验证这些假设，我们建议进行体内研究，以建立一个剂量-时间反应关系的耳毒性作用的锰口服给药大鼠。我们将测试的假设，同时暴露于高水平的连续噪声会加剧听力损伤和耳蜗病理引起的锰。我们还将把听力损害的程度与内耳中锰浓度作为时间、剂量和噪声暴露的函数相关联。为了实现这一点，我们将确定不同剂量的单独锰、单独噪声和锰加噪声引起的听力损伤程度。我们还将比较和评价锰、噪声和锰加噪声组合产生的组织病理学损伤;这将通过评估血管纹、毛细胞和SGN死亡的退化来完成。我们将每种治疗模式的听力损伤程度和耳蜗组织病理学与耳蜗中的Mn浓度相关联。 公共卫生关系：文献中的几份报告描述了听力缺陷的焊工谁是正常暴露于慢性高水平的锰和个人同时暴露于噪声和锰。我们最近发表的研究结果表明，暴露于锰可以导致内耳内的细胞变性，并进一步揭示，这些病变可以引起听觉障碍的大鼠治疗的二价金属。提出的研究的相关性将使我们能够了解锰诱导的听觉丧失的机制，目的是找到新的治疗方法来防止这种情况的发生。