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: 8721345
• 负责人: JEROME Allan ROTH
• 金额: $ 51.09万
• 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/8721345
• 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.

描述（由申请人提供）：锰（Mn）毒性以一系列神经系统症状为特征，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，锰主要是一种职业障碍，最常见于焊接行业，因为焊条含有相对大量的锰。焊枪产生的高温释放出的气体使棒中的锰蒸发，这些锰要么被吸入肺部，随后被输送到循环系统，要么直接通过鼻腔的嗅觉神经元逆行输送到中枢神经系统。流行病学研究和病例报告表明，长期暴露于高水平大气中的锰可导致听力损伤。支持这些临床报告的是我们实验室最近发表的一项研究，该研究首次证明，在大鼠内耳器官型培养中，Mn水平首先损害螺旋神经节神经元，然后损害感觉毛细胞。体内初步研究表明，锰可损害大鼠的听力和耳蜗神经元。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的听力受损，并且听力缺陷会因接触噪音而加剧。由于有报道称锰在急性治疗后会在内耳（耳蜗）中积累，我们假设它有可能损害将声音转化为神经活动的感觉毛细胞或通过听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，我们假设在焊工中观察到的锰致听力损失是由职业工作环境中存在的高水平噪音加剧的。为了验证这些假设，我们建议进行体内研究，以建立口服Mn对大鼠耳毒性作用的剂量-时间反应关系。我们将验证同时暴露于高水平连续噪声会加剧Mn引起的听力损伤和耳蜗病理的假设。我们还将把听力损害程度与内耳锰浓度作为时间、剂量和噪声暴露的函数联系起来。为了做到这一点，我们将确定不同剂量的锰单独、噪音单独和锰加噪音所造成的听力损害程度。我们还将比较和评价Mn、噪声和Mn +噪声组合对组织病理学的损伤；这将通过评估血管纹变性、毛细胞和SGN死亡来完成。我们将耳蜗中Mn浓度与每种治疗模式的听力损伤程度和耳蜗组织病理学相关联。