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利用代谢组学分析探讨丙酸丙酯暴露与气传过敏原致敏和 EASI 评分相关的潜在途径。

The potential pathways underlying the association of propyl-paraben exposure with aeroallergen sensitization and EASI score using metabolomics analysis.

机构信息

Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

Department of Pediatrics, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Republic of Korea.

出版信息

Sci Rep. 2021 Feb 12;11(1):3772. doi: 10.1038/s41598-021-83288-9.

Abstract

Propyl-paraben exposure is associated with aeroallergen sensitization, but its association with atopic dermatitis (AD) is inconclusive. No studies have been conducted on the metabolomic pathways underlying these associations. We investigated the associations between propyl-paraben exposure and aeroallergen sensitization, AD, and Eczema Area and Severity Index (EASI) score and identified the underlying pathways using untargeted metabolomics analysis. We enrolled 455 children in a general population study. Skin prick tests were performed with the assessment of EASI score. Urinary propyl-, butyl-, ethyl-, and methyl-paraben levels were measured. Untargeted metabolomics analysis was performed on the first and fifth urine propyl-paraben quintile groups. The highest urine propyl-paraben quintile group was associated with aeroallergen sensitization, but not with AD. Glycine, threonine, serine, ornithine, isoleucine, arabinofuranose, D-lyxofuranose, citrate, and picolinic acid levels were higher, whereas palmitic acid and 2-palmitoylglycerol levels were lower in the highest quintile propyl-paraben group, than in the lowest quintile group. The propyl-paraben-induced metabolic perturbations were associated with serine and glycine metabolisms, branched-chain amino acid metabolism, and ammonia recycling. Propyl-paraben exposure was associated with aeroallergen sensitization and EASI score, partially via metabolomic changes related with oxidative stress, mTOR, peroxisome proliferator-activated receptors pathway, aryl hydrocarbon receptor signaling pathways, and tricarboxylic acid cycle.

摘要

丙基-paraben 的暴露与气源性过敏原致敏有关,但与特应性皮炎(AD)的关系尚无定论。目前还没有研究针对这些关联的代谢组学途径。我们调查了丙基-paraben 暴露与气源性过敏原致敏、AD 和 Eczema Area and Severity Index(EASI)评分之间的关联,并通过非靶向代谢组学分析确定了潜在途径。我们在一项一般人群研究中招募了 455 名儿童。进行皮肤点刺试验并评估 EASI 评分。测量尿液中的丙基、丁基、乙基和甲基-paraben 水平。对第一和第五尿丙基-paraben 五分位数组进行非靶向代谢组学分析。最高尿丙基-paraben 五分位组与气源性过敏原致敏相关,但与 AD 无关。甘氨酸、苏氨酸、丝氨酸、鸟氨酸、异亮氨酸、阿拉伯呋喃糖、D-木酮糖、柠檬酸和吡啶酸水平较高,而棕榈酸和 2-棕榈酰甘油水平较低在最高五分位数丙基-paraben 组中,低于最低五分位数组。丙基-paraben 引起的代谢紊乱与丝氨酸和甘氨酸代谢、支链氨基酸代谢以及氨循环有关。丙基-paraben 暴露与气源性过敏原致敏和 EASI 评分相关,部分通过与氧化应激、mTOR、过氧化物酶体增殖物激活受体途径、芳香烃受体信号通路和三羧酸循环相关的代谢组学变化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d467/7881090/4f23c4210ed1/41598_2021_83288_Fig1_HTML.jpg

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