Legacy and alternative per- and polyfluoroalkyl substances (PFAS) alter the lipid profile of HepaRG cells

IF 4.8 3区医学 Q1 PHARMACOLOGY & PHARMACY Toxicology Pub Date : 2024-06-10 DOI:10.1016/j.tox.2024.153862

Lackson Kashobwe , Faezeh Sadrabadi , Lars Brunken , Ana Carolina M.F. Coelho , Torkjel M. Sandanger , Albert Braeuning , Thorsten Buhrke , Mattias Öberg , Timo Hamers , Pim.E.G. Leonards

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引用次数: 0

Abstract

Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals used in various industrial and consumer products. They have gained attention due to their ubiquitous occurrence in the environment and potential for adverse effects on human health, often linked to immune suppression, hepatotoxicity, and altered cholesterol metabolism. This study aimed to explore the impact of ten individual PFAS, 3 H-perfluoro-3-[(3-methoxypropoxy) propanoic acid] (PMPP/Adona), ammonium perfluoro-(2-methyl-3-oxahexanoate) (HFPO-DA/GenX), perfluorobutanoic acid (PFBA), perfluorobutanesulfonic acid (PFBS), perfluorodecanoic acid (PFDA), perfluorohexanoic acid (PFHxA), perfluorohexanesulfonate (PFHxS), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), and perfluorooctanesulfonic acid (PFOS) on the lipid metabolism in human hepatocyte-like cells (HepaRG). These cells were exposed to different concentrations of PFAS ranging from 10 µM to 5000 µM. Lipids were extracted and analyzed using liquid chromatography coupled with mass spectrometry (LC- MS-QTOF). PFOS at 10 µM and PFOA at 25 µM increased the levels of ceramide (Cer), diacylglycerol (DAG), N-acylethanolamine (NAE), phosphatidylcholine (PC), and triacylglycerol (TAG) lipids, while PMPP/Adona, HFPO-DA/GenX, PFBA, PFBS, PFHxA, and PFHxS decreased the levels of these lipids. Furthermore, PFOA and PFOS markedly reduced the levels of palmitic acid (FA 16.0). The present study shows distinct concentration-dependent effects of PFAS on various lipid species, shedding light on the implications of PFAS for essential cellular functions. Our study revealed that the investigated legacy PFAS (PFOS, PFOA, PFBA, PFDA, PFHxA, PFHxS, and PFNA) and alternative PFAS (PMPP/Adona, HFPO-DA/GenX and PFBS) can potentially disrupt lipid homeostasis and metabolism in hepatic cells. This research offers a comprehensive insight into the impacts of legacy and alternative PFAS on lipid composition in HepaRG cells.

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传统和替代的全氟烷基和多氟烷基物质（PFAS）会改变 HepaRG 细胞的脂质分布。

全氟和多氟烷基物质（PFAS）是用于各种工业和消费品的合成化学品。由于它们在环境中无处不在，而且可能对人体健康产生不利影响，通常与免疫抑制、肝毒性和胆固醇代谢改变有关，因此备受关注。本研究旨在探讨十种全氟辛烷磺酸（3H-全氟-3-[（3-甲氧基丙氧基）丙酸]（PMPP/Adona）、全氟（2-甲基-3-氧杂己酸）铵（HFPO-DA/GenX）、全氟丁酸（PFBA）、全氟丁基磺酸（PFBS）、全氟癸酸（PFBA）、全氟丁基磺酸（PFBS）、全氟丁基磺酸钠（PFBS）和全氟癸酸（PFBA）对人体健康的影响、全氟癸酸（PFDA）、全氟己酸（PFHxA）、全氟己烷磺酸（PFHxS）、全氟壬酸（PFNA）、全氟辛酸（PFOA）和全氟辛烷磺酸（PFOS）对人肝细胞样细胞（HepaRG）脂质代谢的影响。这些细胞暴露于 10µM 至 5000µM 不同浓度的全氟辛烷磺酸。提取脂质并使用液相色谱-质谱联用仪（LC- MS-QTOF）进行分析。10µM 的 PFOS 和 25µM 的 PFOA 增加了神经酰胺（Cer）、二酰甘油（DAG）、N-乙酰乙醇胺（NAE）、磷脂酰胆碱（PC）和三酰甘油（TAG）脂类的含量，而 PMPP/Adona、HFPO-DA/GenX、PFBA、PFBS、PFHxA 和 PFHxS 则降低了这些脂类的含量。此外，PFOA 和 PFOS 显著降低了棕榈酸（FA 16.0）的水平。本研究显示了全氟辛烷磺酸对各种脂质的不同浓度依赖性影响，揭示了全氟辛烷磺酸对细胞基本功能的影响。我们的研究发现，所调查的传统全氟辛烷磺酸（PFOS、PFOA、PFBA、PFDA、PFHxA、PFHxS 和 PFNA）和替代全氟辛烷磺酸（PMPP/Adona、HFPO-DA/GenX 和 PFBS）可能会破坏肝细胞的脂质稳态和新陈代谢。这项研究全面揭示了传统和替代全氟辛烷磺酸对 HepaRG 细胞脂质组成的影响。

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来源期刊

Toxicology 医学-毒理学

CiteScore

7.80

自引率

4.40%

发文量

222

审稿时长

23 days

期刊介绍： Toxicology is an international, peer-reviewed journal that publishes only the highest quality original scientific research and critical reviews describing hypothesis-based investigations into mechanisms of toxicity associated with exposures to xenobiotic chemicals, particularly as it relates to human health. In this respect "mechanisms" is defined on both the macro (e.g. physiological, biological, kinetic, species, sex, etc.) and molecular (genomic, transcriptomic, metabolic, etc.) scale. Emphasis is placed on findings that identify novel hazards and that can be extrapolated to exposures and mechanisms that are relevant to estimating human risk. Toxicology also publishes brief communications, personal commentaries and opinion articles, as well as concise expert reviews on contemporary topics. All research and review articles published in Toxicology are subject to rigorous peer review. Authors are asked to contact the Editor-in-Chief prior to submitting review articles or commentaries for consideration for publication in Toxicology.