Effect of Complex Mixtures on Oxidative Stress and Cognition in Children

复杂混合物对儿童氧化应激和认知的影响

基本信息

批准号：
10768140
负责人：
Katarzyna Kordas
金额：
$ 1.16万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-18 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10768140
关键词：
Address Administrative Supplement Adolescence Adolescent Affect Age All-Trans-Retinol Anthropometry Antioxidants Area Aromatic Polycyclic Hydrocarbons Arsenic Arylesterase Ascorbic Acid Behavior Biological Biological Markers Blood Blood specimen Buffers Cadmium Carotenoids Characteristics Chemical Exposure Chemicals Child Child Health Childhood Chlorpyrifos Chronic Disease Cognition Communication Complex Complex Mixtures Data Data Analyses Dedications Deoxyguanosine Development Disease Doctor of Philosophy Enrollment Environmental Epidemiology Environmental Exposure Environmental Health Epidemiologist Exposure to F2-Isoprostanes Fasting Funding Future Growth Health Human Immunoassay Income Inductively Coupled Plasma Mass Spectrometry Influentials Knowledge Lead Learning Life Life Cycle Stages Link Measures Metal exposure Metals Methodology Methods Mission Modeling Modification Molecular National Institute of Environmental Health Sciences Neurocognitive Nurses Oxidative Stress Participant Performance Pesticides Phenotype Physical activity Physiological Pilot Projects Prevention Process Public Health Qualifying Questionnaires Recording of previous events Research Research Training Risk Sampling Schools Serum Social Interaction Spottings Strategic Planning Students Testing Time Toxic effect Training Training Programs Urine Uruguay Visit Vitamins Work antioxidant enzyme cognitive ability cognitive function cognitive performance cohort design environmental chemical executive function experience first grade follow-up interest liquid chromatography mass spectrometry machine learning model middle childhood novel oxidative DNA damage pyrethroid response sample collection skills sociodemographics statistical and machine learning summer research urinary

项目摘要

ABSTRACT In many areas of the world, children are regularly exposed to environmental chemicals. During any given pe- riod of life, children will experience exposure to many chemicals at the same time. The effects of such mixtures of chemicals on the molecular underpinnings of the disease process, such as oxidative stress (OS) or on func- tional endpoints such as cognitive functions, are not well understood in children. There is also little understat- ing of the extent to which endogenous antioxidant defenses in children’s bodies or exogenous antioxidants buffer the effects of chemical mixtures on children’s health. The few studies on this topic to date have been mostly cross-sectional or limited to small numbers of chemicals. To address these gaps, the proposed study will leverage the Salud Ambiental Montevideo (SAM) cohort in Uruguay, which has enrolled 679 1st-grade chil- dren between years 2012-19. Currently, children range in age 7-15 years and have been followed-up for 0-5 years, depending on year of enrollment. Exposure to chlorpyrifos and pyrethroids pesticides has been charac- terized in a sub-sample of children using urinary metabolites of the pesticides. Exposure to metals in this co- hort is generally low. In a cross-sectional pilot study of SAM participants, a metal mixture was linked to higher levels of oxidative DNA damage and with lower performance on a test of general cognitive abilities. The pro- posed study will consist of 3 years of follow-up of SAM children to annually characterize the levels of metals in blood and urine, and metabolites of chlorpyrifos, pyrethroids, and polycyclic aromatic hydrocarbons (PAHs) in urine. Each year, urinary biomarkers of OS (F2-isoprostane and 8-OHdG), serum antioxidant enzymes (GPx and PON1), and serum antioxidant vitamins (vitamin C, carotenoids, retinol, etc). will be measured. A sub-sam- ple of ~100 children will participate in a year-long intensive (monthly) assessment of OS biomarkers to charac- terize short-term fluctuations in biomarkers and their biological predictors. Children will complete assessments of executive functions (EF) in Y2 and Y3 of the study. Leveraging data collected at enrollment into SAM (T0, ~7 y), chemical mixtures will be constructed in statistical machine learning models for four time points: T0 and Y1- 3 of the proposed study. These mixtures will be modeled to understand how exposure to mixtures over time is associated with OS and EF. Potential effect modification by antioxidants will be tested. The proposed activities align with the 2018-23 NIEHS strategic plan of research on the exposome to promote human health through the advancement of environmental health sciences. Specifically, they will: 1) advance the basic understanding of short (1 yr) and medium-term (3 yrs) fluctuations in biomarkers of OS and antioxidant defenses, which have not been investigated in children; 2) contribute to understanding of the extent to which chemical mixtures in early-middle childhood affect a molecular process (OS) thought to underlie the development of chronic dis- ease, as well as functional endpoints that underlie children’s learning and social interactions.

抽象的在世界许多地区，儿童在任何特定的时期都会经常接触环境化学物质。在生活的喧嚣中，儿童会同时接触到多种化学物质的混合物。化学物质对疾病过程的分子基础的影响，例如氧化应激（OS）或功能儿童对认知功能等终点的了解还不够深入。儿童体内内源性抗氧化防御或外源性抗氧化剂的程度迄今为止，关于这一主题的研究很少。大部分是横截面的或仅限于少量化学品。为了解决这些差距，拟议的研究。将利用乌拉圭的 Salud Ambiental Montevideo (SAM) 队列，该队列已招收 679 名一年级儿童目前，儿童年龄范围为 7-15 岁，已随访 0-5 岁。年，取决于入学年份。使用农药的尿液代谢物对儿童的子样本进行了测试。在一项针对 SAM 参与者的横断面试点研究中，金属混合物与较高浓度有关。 DNA 氧化损伤水平较低，并且在一般认知能力测试中表现较低。所提出的研究将包括对 SAM 儿童进行为期 3 年的随访，以每年表征体内的金属水平血液和尿液中毒死蜱、拟除虫菊酯和多环芳烃 (PAH) 的代谢物每年尿液中 OS（F2-异前列腺素和 8-OHdG）、血清抗氧化酶（GPx）的尿液生物标志物。和 PON1），以及血清抗氧化维生素（维生素 C、类胡萝卜素、视黄醇等）。约 100 名儿童将参加为期一年的 OS 生物标志物强化（每月）评估，以评估其特征确定生物标志物及其生物预测因子的短期波动儿童将完成评估。利用参加 SAM 时收集的数据（T0，~7）。 y)，化学混合物将在四个时间点的统计机器学习模型中构建：T0 和 Y1- 将对这些混合物进行建模，以了解随着时间的推移暴露于混合物的情况。将测试与 OS 和 EF 相关的抗氧化剂的潜在影响。与 2018-23 NIEHS 暴露组研究战略计划保持一致，通过以下方式促进人类健康具体来说，他们将：1）增进基本认识。 OS 和抗氧化防御生物标志物的短期（1 年）和中期（3 年）波动， 2) 有助于了解化学混合物在多大程度上童年早期影响一个被认为是慢性疾病发展基础的分子过程（OS）轻松性，以及构成儿童学习和社交互动基础的功能终点。