Pilot assessment of the effects of noise, lead, and cadmium on hearing in mice

噪音、铅和镉对小鼠听力影响的初步评估

• 批准号: 8688986
• 负责人: Richard L Neitzel
• 金额: $ 7.78万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2015-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8688986
• 关键词: Accounting; Address; Adult; Adverse effects; Affect; Animal Model; Animals; Area; Auditory; Auditory Brainstem Responses; Auditory Threshold; CBA/J Mouse; Cadmium; Cell Count; Centers for Disease Control and Prevention (U.S.); Child; Chronic; Collection; Data; Developed Countries; Developing Countries; Development; Disease; Dizziness; Dose; Environment; Environmental Exposure; Environmental Pollution; Epidemiologic Studies; Equilibrium; Exposure to; Femur; Future; Goals; Guidelines; Hair Cells; Health; Healthy People 2020; Hearing; Heavy Metals; Human; Lead; Learning; Link; Measures; Metals; Mus; National Institute on Deafness and Other Communication Disorders; Noise; Occupational; Organic solvent product; Outcome; Performance; Pharmacologic Substance; Public Health; Quality of life; Research; Risk; Science; Series; Serum; Solvents; Swimming; System; Testing; Time; United States; Work; base; blood lead; bone; drinking water; hearing impairment; insight; lead exposure; otoacoustic emission; prevent; programs; psychologic; public health relevance; response; social; therapy design; uptake; young adult

DESCRIPTION (provided by applicant): Hearing loss - a very common condition affecting hundreds of millions of people globally - has substantial adverse impact on human health and quality of life, and is associated with a wide variety of adverse social, psychological, and occupational consequences. It also has a substantial impact on learning outcomes and intellectual development in children. A potentially important but not well-researched cause of hearing loss is exposure to environmental contaminants, and in particular heavy metals. A limited but highly suggestive body of research suggests that exposures to lead (Pb) and cadmium (Cd) - both common environmental contaminants in the United States and worldwide - may be associated with an increased risk of hearing loss. However, no causal link has yet been established between exposure to heavy metals and hearing loss. Moreover, adverse effects of environmental contaminants (e.g., organic solvents) can be aggravated by concurrent exposure to noise which is present in many environments contaminated with heavy metals. Such interactions have not been explored for Pb or Cd. The proposed study will evaluate and quantify, in a well- understood animal model (CBA/J mice), the relationship between Pb and Cd exposure and hearing damage. The first hypothesis is that exposure to Pb and Cd will be associated with a risk of hearing and vestibular damage. To evaluate this hypothesis we will expose groups of young mice to varying doses of Pb or Cd in their drinking water for a period of 8 weeks, achieving serum levels commonly found in humans in contaminated areas. We will quantitatively evaluate animals' auditory thresholds at baseline and at the midpoint and end of the exposure period via Auditory Brainstem Response (ABR) and Distortion Product Otoacoustic Emissions (DPOAEs). We will also evaluate vestibular function at the same time points. At the conclusion of the study we will conduct cochlear hair cell counts to enumerate cochlear damage, and will analyze Pb levels in the ossicles and other selected bones as an additional measure of Pb exposure. The second hypothesis is that a combination of noise and Pb or Cd will result in a greater hearing loss than exposure to noise or metals alone. To evaluate synergistic or additive effects of these agents we will measure auditory deficits resulting from noise exposure alone or in combinations with Pb or Cd. This project addresses two of NIDCD's focus areas (hearing loss and balance); improvements in health in these areas, such as those that might ultimately results from the proposed work, are also goals of the Healthy People 2020 program. Successful collection of pilot data in the proposed study will result in a subsequent R01 application to NIDCD. The results of this study may help guide future public health interventions designed to reduce the burden of hearing loss through reductions in environmental exposures to heavy metals.

描述（由申请人提供）：听力损失是一种非常常见的疾病，影响全球数亿人，对人类健康和生活质量有重大不利影响，并与各种不良的社会，心理和职业后果有关。它还对儿童的学习成果和智力发展产生重大影响。听力损失的一个潜在重要但尚未得到充分研究的原因是暴露于环境污染物，特别是重金属。一项有限但高度暗示性的研究表明，铅（Pb）和镉（Cd）-美国和世界范围内常见的环境污染物-可能与听力损失风险增加有关。然而，尚未确定接触重金属和听力损失之间的因果关系。此外，环境污染物的不利影响（例如，有机溶剂）可因同时暴露于噪声而加重，噪声存在于许多被重金属污染的环境中。这种相互作用尚未探讨铅或镉。拟议的研究将评估和量化，在一个很好理解的动物模型（CBA/J小鼠），铅和镉暴露和听力损伤之间的关系。第一个假设是，铅和镉的暴露将与听力和前庭损伤的风险。为了评估这一假设，我们将暴露组的年轻小鼠不同剂量的铅或镉在他们的饮用水为期8周，达到血清中常见的污染地区的人类。我们将通过听觉脑干反应（ABR）和畸变产物耳声发射（DPOAE）定量评估动物在基线和暴露期中点和结束时的听阈。我们还将在同一时间点评估前庭功能。在研究结束时，我们将进行耳蜗毛细胞计数，以列举耳蜗损伤，并将分析铅水平的听骨和其他选定的骨骼作为铅暴露的额外措施。第二个假设是，噪声和铅或镉的组合将导致比单独暴露于噪声或金属更大的听力损失。为了评估这些药物的协同或相加作用，我们将测量单独或与铅或镉组合的噪声暴露引起的听觉缺陷。该项目涉及NIDCD的两个重点领域（听力损失和平衡）;改善这些领域的健康状况，例如可能最终由拟议工作产生的健康状况，也是2020年健康人计划的目标。在拟议的研究中成功收集试验数据将导致随后将R 01应用于NIDCD。这项研究的结果可能有助于指导未来的公共卫生干预措施，旨在通过减少重金属的环境暴露来减轻听力损失的负担。