作为阻燃剂和增塑剂使用的有机酸影响H295R上腺细胞表型和功能
Zixuan Li1, Bernard Robaire1,2, Barbara F Hales1
1Department of Pharmacology & Therapeutics, McGill University, Montreal, QC, H3G 1Y6, Canada.
Endocrinology
|July 31, 2023
概括
替代阻燃剂的有机酸 (OPEs) 可能会影响上腺功能. 研究表明,OPEs改变了上腺细胞功能,类固醇生产和基因表达,这表明上腺是这些化学物质的关键目标.
科学领域:
- 内分泌学 在内分泌学.
- 毒理学 毒理学 毒理学
- 细胞生物学 细胞生物学
背景情况:
- 由于不良影响,制阻燃剂 (BFR) 受到监管.
- 有机酸 (OPEs) 正在取代BFR,但它们的内分泌干扰潜力尚未得到充分研究.
- 上腺在内分泌功能中的作用使其成为评估化学毒性的关键目标.
研究的目的:
- 研究OPE对人类上腺H295R细胞的影响.
- 为了比较OPEs对上腺细胞功能的影响与遗留的BFR,BDE-47.
- 确定特定的OPE及其影响类固醇生成的机制.
主要方法:
- 对暴露于OPE和BDE-47.7的H295R细胞进行高含量查.
- 评估了细胞毒性,氧化应激,线粒体,溶酶体和脂质滴滴变化.
- 评估了类固醇激素的产生 (皮质醇,阿尔多斯特) 和类固醇酶的基因表达.
主要成果:
- 大多数OPE降低了氧化应激和改变了有机细胞含量 (线粒体,溶解体,脂质滴).
- 三烯-OPEs (IPPP,TMPP,TPHP) 和TDCIPP的效果比BDE-47更强.
- IPPP增加了基底皮质醇和阿尔多,而TPHP和TMPP降低了它们;STAR表达变化与类固醇生产相关.
结论:
- OPEs,特别是三-OPEs,对上腺细胞表现出强烈的影响.
- 上腺是OPE内分泌干扰的重要目标.
- 改变了类固醇酶的表达,如CYP11B1和CYP11B2,以及STAR调解了OPE对激素产生的影响.
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