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研究邻苯二甲酸酯类环境毒物与脂质结构的相互作用。

Investigating interactions of phthalate environmental toxicants with lipid structures.

作者信息

Bailey-Hytholt Christina M, Puranik Tanaya, Tripathi Anubhav, Shukla Anita

机构信息

School of Engineering, Center for Biomedical Engineering, Institute for Molecular and Nanoscale Innovation, Brown University, Providence, RI, United States.

School of Engineering, Center for Biomedical Engineering, Institute for Molecular and Nanoscale Innovation, Brown University, Providence, RI, United States.

出版信息

Colloids Surf B Biointerfaces. 2020 Jun;190:110923. doi: 10.1016/j.colsurfb.2020.110923. Epub 2020 Mar 2.

DOI:10.1016/j.colsurfb.2020.110923
PMID:32199260
Abstract

Di(2-ethylhexyl) phthalate (DEHP) is one of the most abundant plasticizers in common household products. It leaches from materials, resulting in exposure associated with detrimental health effects. The main objective of this study was to investigate how DEHP and its metabolite, mono(2-ethylhexyl) phthalate (MEHP), interact with and permeate lipid structures, namely vesicles and planar bilayers. Using dynamic light scattering, we observed significant changes in the size and polydispersity of L-α-phosphatidylcholine (egg PC) vesicles when incubated with DEHP but not MEHP at the same concentrations (100 and 200 μM). We demonstrated that these effects are mitigated by pre-treatment with chitosan nanoparticles which adsorb the phthalates. Using quartz crystal microbalance with dissipation monitoring (QCM-D), we observed a concentration dependence on the interaction of DEHP with egg PC supported lipid bilayers (SLBs). QCM-D results suggested lipid removal for 5 and 100 μM DEHP, and adsorption and potential embedment in the bilayer at 50 and 200 μM DEHP. SLB mass decrease was observed for all concentrations of MEHP (5, 50, 100, and 200 μM), suggesting lipid removal. We also investigated the permeability of DEHP and MEHP as well as several small molecules across a 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) suspended lipid bilayer. We found that DEHP and MEHP both had low permeabilities, but only DEHP remained associated with the bilayer. Exposure to DEHP and MEHP influenced how several common small molecules interacted with DOPC bilayers. Ultimately, this work provides insight into mechanisms of phthalate interactions with lipid structures, having implications for human health.

摘要

邻苯二甲酸二(2-乙基己基)酯(DEHP)是常见家用产品中含量最高的增塑剂之一。它会从材料中渗出,导致接触并产生有害健康影响。本研究的主要目的是研究DEHP及其代谢物单(2-乙基己基)邻苯二甲酸酯(MEHP)如何与脂质结构(即囊泡和平面双层膜)相互作用并渗透其中。通过动态光散射,我们观察到当与相同浓度(100和200μM)的DEHP而非MEHP孵育时,L-α-磷脂酰胆碱(鸡蛋PC)囊泡的大小和多分散性发生了显著变化。我们证明,用吸附邻苯二甲酸盐的壳聚糖纳米颗粒进行预处理可减轻这些影响。使用带耗散监测的石英晶体微天平(QCM-D),我们观察到DEHP与鸡蛋PC支撑脂质双层膜(SLB)相互作用存在浓度依赖性。QCM-D结果表明,5和100μM的DEHP会导致脂质去除,而50和200μM的DEHP会吸附并可能嵌入双层膜中。对于所有浓度的MEHP(5、50、100和200μM),均观察到SLB质量下降,表明有脂质去除。我们还研究了DEHP和MEHP以及几种小分子在1,2-二油酰基-sn-甘油-3-磷酸胆碱(DOPC)悬浮脂质双层膜中的渗透性。我们发现DEHP和MEHP的渗透性都很低,但只有DEHP与双层膜保持关联。暴露于DEHP和MEHP会影响几种常见小分子与DOPC双层膜的相互作用。最终,这项工作深入了解了邻苯二甲酸盐与脂质结构的相互作用机制,对人类健康具有重要意义。

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