尿中フタル酸代謝物と喘息及び酸化ストレスとの関連

尿邻苯二甲酸酯代谢物与哮喘和氧化应激的关系

基本信息

批准号：
20J10766
负责人：
KETEMA RAHEL MESFIN
金额：
$ 1.09万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for JSPS Fellows
财政年份：
2020
资助国家：
日本
起止时间：
2020-04-24 至 2022-03-31
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-20J10766/
关键词：
Biomonitoring Phthalate esters School children Allergies Oxidative stress markers phthalates exposure children exposure trend Lifestyle behaviors biomonitoring regulation

项目摘要

Urine was collected from 7-year-old children participating in the Hokkaido birth cohort, and 10 metabolites of 4 phthalate compounds were measured by UPLC-MS/MS. Levels of 3 oxidative stress markers (8-OHdG, HEL, HNE)) were measured by ELISA kits. ISAAC questionnaire completed by parents of the child used to define wheeze, rhino conjunctivitis, and eczema.All metabolites were detected in > 96% of samples. Highest detection was in MECPP, MnBP, and MEHHP with median 37.4 ng/mL, 36.8 ng/mL, and 25.8 ng/mL, respectively. No exposure change was observed in these phthalate metabolites from 2012 to 2017. The Japan phthalate ester regulation revised in 2010 in toys and food containers related to children could not alter the phthalates exposure change. Individual phthalate metabolites, MECPP (OR = 1.41) and cx-MINP (OR = 1.40) increased the risk of wheeze. In a mixed exposure analysis, the Weighted Quantile Sum index showed significant association (OR = 1.46) with wheeze and (OR = 1.40) eczema. The Bayesian Kernel Machine Regression model, DINP metabolites showed the highest group posterior inclusion probability (PIP). Among DINP metabolites, MINP in wheeze, cx-MINP in rhino-conjunctivitis and OH-MINP in eczema showed the highest conditional PIPs. The overall metabolites mixture effect was associated with eczema. On the contrary, no mediation of oxidative stress was observed in the association between phthalates and symptoms, which may be due to low oxidative stress. Participants in this study were only 7 years old, demonstrating the importance of continuing the study in the future.

收集参加北海道出生队列的 7 岁儿童的尿液，通过 UPLC-MS/MS 测定 4 种邻苯二甲酸酯化合物的 10 种代谢物。通过 ELISA 试剂盒测量 3 种氧化应激标记物（8-OHdG、HEL、HNE）的水平。由儿童家长填写的 ISAAC 问卷用于定义喘息、犀牛结膜炎和湿疹。> 96% 的样本中检测到所有代谢物。 MECPP、MnBP 和 MEHHP 的检测量最高，中位数分别为 37.4 ng/mL、36.8 ng/mL 和 25.8 ng/mL。 2012年至2017年期间，未观察到这些邻苯二甲酸酯代谢物的暴露量变化。2010年修订的日本邻苯二甲酸酯法规中与儿童有关的玩具和食品容器不能改变邻苯二甲酸酯暴露量的变化。个别邻苯二甲酸酯代谢物 MECPP (OR = 1.41) 和 cx-MINP (OR = 1.40) 会增加喘息的风险。在混合暴露分析中，加权分位数总和指数显示与喘息和湿疹（OR = 1.40）显着相关（OR = 1.46）。贝叶斯核机器回归模型中，DINP 代谢物显示出最高的组后验包含概率 (PIP)。在 DINP 代谢物中，喘息中的 MINP、鼻结膜炎中的 cx-MINP 和湿疹中的 OH-MINP 显示出最高的条件 PIP。总体代谢物混合物效应与湿疹相关。相反，在邻苯二甲酸盐与症状之间的关联中没有观察到氧化应激的介导，这可能是由于低氧化应激所致。这项研究的参与者只有 7 岁，这表明了未来继续研究的重要性。