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.

从参加北海道出生队列的7岁儿童中收集尿液，通过UPLC-MS/MS测量10种邻苯二甲酸酯化合物的10代谢产物。通过ELISA试剂盒测量了3个氧化应激标记（8-OHDG，HEL，HNE）的水平。艾萨克问卷是由用来定义喘息的孩子的父母完成的，犀牛结膜炎和湿疹。在> 96％的样本中检测到了所有代谢物。最高检测分别为MECPP，MNBP和MEHHP，中位数为37.4 ng/ml，36.8 ng/ml和25.8 ng/ml。从2012年到2017年，这些邻苯二甲酸酯代谢产物中未观察到暴露变化。日本邻苯二甲酸酯调节在2010年在与儿童有关的玩具和食品容器中修订了邻苯二甲酸酯，无法改变邻苯二甲酸酯的暴露变化。单个邻苯二甲酸盐代谢物，MECPP（OR = 1.41）和CX-MINP（OR = 1.40）增加了喘息的风险。在混合的暴露分析中，加权分位数和（OR = 1.46）与喘息和（OR = 1.40）的湿疹显示出显着的关联（OR = 1.46）。 DINP代谢产物的贝叶斯内核回归模型显示出最高的组后纳入概率（PIP）。在DINP代谢产物中，喘息的MINP，犀牛连接性炎的CX-MINP和湿疹中的OH-Minp显示出最高的条件性PIP。总体代谢物混合物效应与湿疹有关。相反，在邻苯二甲酸酯和症状之间的关联中未观察到氧化应激的介导，这可能是由于氧化应激低。这项研究的参与者只有7年的历史，表明将来继续进行研究的重要性。