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孕妇三个孕期尿液中的对羟基苯甲酸酯衍生物:变异性、预测因素及与氧化应激生物标志物的关联。

Urinary paraben derivatives in pregnant women at three trimesters: Variability, predictors, and association with oxidative stress biomarkers.

机构信息

Key Laboratory of Environment and Health (HUST), Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China.

Institute of Environmental Health, Wuhan Centers for Disease Control & Prevention, Wuhan, Hubei 430024, PR China.

出版信息

Environ Int. 2022 Jul;165:107300. doi: 10.1016/j.envint.2022.107300. Epub 2022 May 16.

DOI:10.1016/j.envint.2022.107300
PMID:35635959
Abstract

Exposure to parabens has been shown to increase oxidative stress, which has a vital impact on the development of numerous diseases. However, few studies reported the effects of the paraben derivatives on oxidative stress, particularly among pregnant women. This study, using repeated measurements, aimed to understand the exposure profiles of urinary paraben derivative concentrations and their relationships with oxidative stress biomarkers (OSBs). A total of 861 pregnant women, who provided spot urine samples at three trimesters, were included, and 2583 urine samples were used to measure four paraben derivatives [p-hydroxybenzoic acid (p-HB), 3,4-dihydroxybenzoic acid (3,4-DHB), methyl protocatechuate, and ethyl protocatechuate], four parabens (methyl, ethyl, propyl, and butyl), and three OSBs [8-hydroxy-2'-deoxyguanosine (for DNA), 8-hydroxyguanosine (for RNA), and 4-hydroxy nonenal mercapturic acid (for lipid)]. Pregnant women were extensively exposed to parabens and paraben derivatives with detection frequencies (DFs) of 86.1%-100%, except for butylparaben with a DF of 14.9%. p-HB and 3,4-DHB had relatively high urinary concentrations (specific gravity-adjusted median values: 1394 and 74.5 ng/mL, respectively). Low reproducibility in paraben derivatives was found across the three trimesters. Sampling season, pre-pregnancy body mass index, and infant sex were predictors of some paraben derivatives/parabens. Linear mixed model analyses showed that all target compounds (if DF > 50%) were associated with increases in all the selected OSBs, where the percent change in OSBs with an interquartile range increase in paraben concentration ranged from 9.85% to 24.7%, while those in paraben derivative concentration ranged from 13.8% to 72.1%. Weighted quantile sum model showed that joint exposure was significantly associated with increased OSBs, and paraben derivatives were stronger contributors to OSBs compared with parabens. Overall, urinary paraben derivatives were associated with increased oxidative stress of nucleic acids and lipid in pregnant women.

摘要

对苯二甲酸酯类物质的暴露已被证实会增加氧化应激,这对许多疾病的发展有重要影响。然而,很少有研究报告了对苯二甲酸酯类物质衍生物对氧化应激的影响,特别是在孕妇中。本研究采用重复测量的方法,旨在了解尿中对苯二甲酸酯类物质衍生物浓度的暴露概况及其与氧化应激生物标志物(OSBs)的关系。共有 861 名孕妇在三个孕期采集了尿液样本,共采集了 2583 份尿液样本,用于测量四种对苯二甲酸酯类物质衍生物[对羟基苯甲酸(p-HB)、3,4-二羟基苯甲酸(3,4-DHB)、甲基原儿茶酸和乙基原儿茶酸]、四种对苯二甲酸酯[甲基、乙基、丙基和丁基]和三种 OSBs[8-羟基-2'-脱氧鸟苷(用于 DNA)、8-羟基鸟苷(用于 RNA)和 4-羟基壬烯醛巯基尿酸(用于脂质)]。除了丁基对苯二甲酸酯的检测频率(DF)为 14.9%外,孕妇广泛接触到对苯二甲酸酯和对苯二甲酸酯类物质衍生物,其 DF 为 86.1%-100%。p-HB 和 3,4-DHB 的尿液浓度相对较高(比重校正后的中位数分别为 1394 和 74.5ng/mL)。在三个孕期中,对苯二甲酸酯类物质衍生物的重现性较差。采样季节、孕前体重指数和婴儿性别是一些对苯二甲酸酯类物质/对苯二甲酸酯的预测因子。线性混合模型分析表明,所有目标化合物(如果 DF>50%)均与所有选定的 OSBs 增加有关,其中 OSB 与对苯二甲酸酯浓度的中值范围增加 1 个四分位距的百分比变化范围为 9.85%-24.7%,而对苯二甲酸酯衍生物浓度的百分比变化范围为 13.8%-72.1%。加权分位数总和模型表明,联合暴露与 OSBs 的增加显著相关,与对苯二甲酸酯相比,对苯二甲酸酯衍生物对 OSBs 的贡献更大。总的来说,孕妇尿液中对苯二甲酸酯类物质衍生物与核酸和脂质的氧化应激增加有关。

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