Models for Assessing Risk of Occupational Hearing Loss

描述（由申请人提供）：听力损失是美国最常见的职业伤害。超过3000万工人暴露在潜在的危险噪音中，900万工人暴露在耳毒性化学品中。这项资助的重点是确定化学窒息剂增强噪声诱发听力的机制和条件 损失（NIHL）。化学窒息作为有用的模型化合物，因为氰化氢和一氧化碳加强NIHL大鼠在暴露水平相关的工作场所。消防员、重型设备操作员、隧道和收费工人以及卡车司机同时暴露在噪音和化学窒息物中。一个两阶段的假设将进行测试，噪音和窒息剂“启动”活性氧（ROS）的产生和窒息剂“促进”这种压力，通过损害内在的ROS缓冲机制。将使用电生理和声学方法比较治疗组之间的髋关节功能。通过琥珀酸脱氢酶活性染色检测相应的组织病理学损伤。在增强和抑制内源性ROS缓冲的药物治疗后，将评估窒息剂暴露对NIHL的增强作用 系统.如果ROS促进是增强NIHL的关键，那么增强ROS清除的治疗将降低易感性。此外，减少ROS清除的治疗将增加易感性。生化研究将证实药物治疗对内在ROS缓冲的有效性。将使用电子顺磁自旋共振光谱法（EPR）直接测量耳蜗中的ROS。最后，免疫组织化学方法将被用来定义混合曝光的后果，在耳蜗选定的压力途径。

DESCRIPTION (provided by applicant): Hearing loss is the most common occupational injury in the United States. More than 30 million workers are exposed to potentially hazardous noise and 9 million workers have exposure to ototoxic chemicals. The focus of this grant is identifying the mechanisms and conditions under which chemical asphyxiates potentiate noise induced hearing loss (NIHL). Chemical asphyxiates serve as useful model compounds because hydrogen cyanide and carbon monoxide potentiate NIHL in rats at exposure levels relevant to the workplace. Fire fighters, operators of heavy equipment, tunnel and toll workers, and truck drivers are exposed to noise and chemical asphyxiants simultaneously. A two-stage hypothesis will be tested whereby noise and asphyxiant "initiate" reactive oxygen species (ROS) generation and asphyxiants "promote" this stress by impairing intrinsic ROS buffering mechanisms. Cochlear function will be compared among treatment groups using electrophysiological and acoustic methods. Corresponding histopathological injury will be detected by staining for succinate dehydrogenase activity. Potentiation of NIHL by asphyxiant exposure will be assessed following pharmacological treatments that enhance and depress intrinsic ROS buffering systems. If ROS promotion is critical to potentiation of NIHL, then treatments that enhance ROS scavenging will reduce susceptibility. Also, treatments that decrease ROS scavenging will increase susceptibility. Biochemical studies will confirm the effectiveness of drug treatment on intrinsic ROS buffering. Direct measurement of ROS will be performed in the cochlea using electron paramagnetic spin resonance spectrometry (EPR). Finally, immunohistochemical methods will be used to define the consequences of mixed exposures on selected stress pathways in the cochlea.