Neurotoxic and neurodegenerative risks from chronic exposure to metal mixtures in e-cigarette aerosol

长期接触电子烟气溶胶中的金属混合物会产生神经毒性和神经退行性风险

基本信息

批准号：
10883865
负责人：
Markus Hilpert
金额：
$ 7.32万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-01 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10883865
关键词：
Address Adolescent Adolescent and Young Adult Adverse effects Aerosols Affect Air Aldehydes Analytical Chemistry Animal Model Animals Area Authorization documentation Blood Brain Calcium Carcinogens Cardiac Myocytes Cardiovascular Diseases Cardiovascular system Cell Culture Techniques Cell model Cessation of life Characteristics Chromium Chronic Cigarette Clinical Cognition Cognitive deficits Copper Corpus striatum structure Cotinine Data Devices Disease Disease model Dose Electronic cigarette Environmental Engineering technology Epidemiology Etiology Exhibits Exposure to Flavoring General Population Genetic Determinism Genetic Predisposition to Disease Glycerol Health Health Hazards Heating Human Image Impaired cognition Individual Inductively Coupled Plasma Mass Spectrometry Inhalation Iron Knock-in Knowledge LRRK2 gene Laboratories Lead levels Length Link Liquid substance Manganese Measures Mediating Metal exposure Metals Motor Mus Mutation Nerve Degeneration Neurites Neurodegenerative Disorders Neurons Neurotoxins Nickel Nicotine Parkinson Disease Pathologic Patients Perception Phase Policy Maker Predisposition Propylene Glycols Public Health Recording of previous events Reporting Research Personnel Respiratory Disease Risk Role Sampling Selenium Smoker Smoking Solvents Synapses System Testing Tobacco Toxic effect Vanadium Youth Zinc authority base brain health brain tissue cancer risk carcinogenicity density disorder risk dopaminergic neuron e-cigarette aerosols electronic cigarette use electronic cigarette user electronic liquid exposed human population human subject induced pluripotent stem cell motor deficit motor impairment mouse model neurotoxic neurotoxicity novel operation particle premature prevent respiratory secondhand aerosol sporadic Parkinson&apos s Disease tobacco smokers vaping vapor

项目摘要

PROJECT SUMMARY Electronic cigarettes (e-cigs), battery-operated devices that heat liquids to generate an inhaled aerosol vapor, are increasingly popular, especially among younger users. E-cigs are seen as an increasingly attractive alternative to tobacco cigarettes; however, little is known about the human health effects arising from chronic exposure to these aerosols. A growing number of studies have examined potential e-cig risks for cancer, respiratory, and cardiovascular diseases. New data from our laboratory and others, however, raise additional human health concerns about exposure to potentially neurotoxic metals released from the heated coil wire and other e-cig components. For example, we found that in a large fraction e-cig aerosol samples we collected, nickel, chromium, and lead levels exceeded EPA national ambient air quality standards or ATSDR minimum risk levels (MRL). Notably, this was true for manganese (Mn), a prime suspect in sporadic Parkinson’s disease (PD) etiology. Others have found that vanadium, copper and selenium (all suspected for a potential role in PD) were higher in blood of e-cig users as compared to tobacco smokers. We hypothesize that hazardous metals released by e-cigs may accumulate in the brain and pose significant neurotoxic risk(s) for neurodegenerative diseases upon chronic exposure. We will test our hypothesis in three ways. First, we will determine the levels of potentially neurotoxic metals in the aerosol produced by several popular e-cigs operated under different conditions and with e-liquids differing in flavor and nicotine content. Second, we will examine the neurotoxic effect of chronic e-cig aerosol exposure in neuronal cell cultures derived from human subjects carrying incompletely-penetrant mutations linked to PD or from healthy controls, and identify metal mixtures of particular neurotoxic concern. Third, we will measure metal concentrations in brain tissue of chronically e-cig exposed mice, which are wildtype controls or knock-in for a mutation that increases the risk for PD; we will also determine the metals’ potential adverse effects on motor function and cognition in the mouse models. Findings from this study are likely to provide crucial and heretofore unavailable information to policy makers and will enable them to evaluate potential neurotoxic health risks arising from second-hand exposure to e-cig aerosol. We hypothesize that health risks are significantly influenced by genetic susceptibility to neurodegenerative disease, as well as by e-cig device construction, operating conditions, e-liquid flavoring, and nicotine content.

项目概要电子烟（e-cigs）、加热液体以产生吸入气溶胶蒸气的电池供电设备，越来越受欢迎，尤其是在年轻用户中，电子烟被视为越来越有吸引力。香烟的替代品；然而，人们对慢性香烟对人类健康的影响知之甚少。越来越多的研究已经研究了电子烟潜在的癌症风险，然而，我们实验室和其他实验室的新数据提出了更多的建议。人类健康担心接触从加热线圈中释放出的潜在神经毒性金属，例如，我们发现在我们收集的大部分电子烟气溶胶样本中，镍、铬和铅含量超过 EPA 国家环境空气质量标准或 ATSDR 最低标准值得注意的是，锰 (Mn) 是导致散发性帕金森病的主要因素。 (PD) 病因学其他人发现钒、铜和硒（都怀疑在 PD 中具有潜在作用）与吸烟者相比，电子烟使用者的血液中的有害金属含量更高。电子烟释放的物质可能会在大脑中积聚，并对神经退行性疾病造成重大的神经毒性风险我们将通过三种方式检验我们的假设：首先，我们将确定水平。几种流行电子烟在不同条件下操作时产生的气溶胶中潜在神经毒性金属的含量其次，我们将检查神经毒性。慢性电子烟气溶胶暴露对人类受试者神经元细胞培养物的影响与 PD 或健康对照相关的不完全渗透突变，并识别特定的金属混合物第三，我们将测量长期接触电子烟的脑组织中的金属浓度。小鼠，它们是野生型对照或敲入突变，会增加 PD 风险；确定金属对小鼠模型运动功能和认知的潜在不利影响。这项研究可能会为政策制定者提供迄今为止无法获得的重要信息，并将使他们能够评估因二手电子烟气溶胶接触而产生的潜在神经毒性健康风险。我们认为，神经退行性疾病的遗传易感性对健康风险有显着影响疾病，以及电子烟设备构造、操作条件、电子烟液调味和尼古丁含量。