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脂肪细胞中氯化石蜡的积累取决于细胞脂质含量和氯化水平。

Accumulation of chlorinated paraffins in adipocytes is determined by cellular lipid content and chlorination level.

作者信息

Vrzáčková Nikola, Tomáško Jakub, Svoboda Petr, Škop Vojtěch, Melčová Magdalena, Dudová Jana, Zelenka Jaroslav, Pulkrabová Jana, Ruml Tomáš

机构信息

Department of Biochemistry and Microbiology, University of Chemistry and Technology, Technická 3, 16000, Prague, Czech Republic.

Department of Food Analysis and Nutrition, University of Chemistry and Technology, Technická 3, 16000, Prague, Czech Republic.

出版信息

Arch Toxicol. 2025 Mar;99(3):1117-1131. doi: 10.1007/s00204-024-03956-3. Epub 2025 Jan 10.

Abstract

Chlorinated paraffins (CPs) are environmental pollutants extensively used in industries. While the use of short-chain chlorinated paraffins (SCCPs) has been restricted since 2017, the use of medium-chain chlorinated paraffins (MCCPs) has risen as their replacement. Due to lipophilic character, it can be expected that CPs enter the cells; however, the in vitro accumulation potential of CPs remains poorly understood. In this study, we aimed to explore the ability of SCCPs and MCCPs to accumulate in fat cells. We utilized an in vitro model of mouse 3T3-L1 preadipocytes and adipocytes. Using gas chromatography coupled with high-resolution mass spectrometry operated in negative chemical ionization mode, we determined the intracellular amounts of CPs. These compounds accumulated at rates of 8.5 ± 0.1 µg/g/h for SCCPs and 7.8 ± 0.3 µg/g/h for MCCPs when an initial concentration of 120 ng/ml was present in the medium. This rate increased approximately tenfold when the concentration of CPs was raised to 1200 ng/ml. CPs content in adipocytes steadily increased over 5 days, whereas preadipocytes accumulated 15-20 times less CPs. This highlights the importance of cellular lipid content, which was about 12 times higher in adipocytes. Furthermore, we found that the level of chlorine content in the CPs molecules significantly influenced their accumulation. Our results demonstrate that MCCPs exhibit a similar accumulation potential to SCCPs, with lipid content playing a crucial role. As with SCCPs, restrictions on the use of MCCPs in industry should be considered to mitigate their environmental and health impacts.

摘要

氯化石蜡(CPs)是广泛应用于工业的环境污染物。自2017年以来,短链氯化石蜡(SCCPs)的使用已受到限制,而中链氯化石蜡(MCCPs)作为其替代品,使用量有所上升。由于具有亲脂性,可以预期CPs会进入细胞;然而,CPs的体外积累潜力仍知之甚少。在本研究中,我们旨在探究SCCPs和MCCPs在脂肪细胞中的积累能力。我们使用了小鼠3T3-L1前脂肪细胞和脂肪细胞的体外模型。通过在负化学电离模式下运行的气相色谱-高分辨率质谱联用技术,我们测定了细胞内CPs的含量。当培养基中初始浓度为120 ng/ml时,这些化合物的积累速率分别为:SCCPs为8.5±0.1 μg/g/h,MCCPs为7.8±0.3 μg/g/h。当CPs浓度提高到1200 ng/ml时,该速率增加了约10倍。脂肪细胞中的CPs含量在5天内稳步增加,而前脂肪细胞积累的CPs量则少15至20倍。这突出了细胞脂质含量的重要性,脂肪细胞中的脂质含量约高12倍。此外,我们发现CPs分子中的氯含量水平对其积累有显著影响。我们的结果表明,MCCPs与SCCPs具有相似的积累潜力,脂质含量起着关键作用。与SCCPs一样,应考虑限制MCCPs在工业中的使用,以减轻其对环境和健康的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ac1/11821709/028531f50e7d/204_2024_3956_Fig1_HTML.jpg

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