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新型溴化阻燃剂1,2-双（2,4,6-三溴苯氧基）乙烷（BTBPE）对甲状腺干扰的体外和体内研究

An In Vitro and In Vivo Study of Thyroid Disruption of 1,2-Bis(2,4,6-tribromophenoxy)ethane (BTBPE)-A Novel Brominated Flame Retardant.

作者信息

Zheng Na, Li Na, Lei Lei, Zhu Biran, Qiao Kun, Wang Qiangwei, Liang Chengqian, Guo Yongyong, Yang Lihua, Han Jian, Zhou Yuxi, Zhou Bingsheng

机构信息

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, P. R. China.

University of Chinese Academy of Sciences, Beijing 100049, P. R. China.

出版信息

Environ Health (Wash). 2023 Nov 13;2(1):42-51. doi: 10.1021/envhealth.3c00140. eCollection 2024 Jan 19.

DOI:10.1021/envhealth.3c00140
PMID:39473485
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11504562/
Abstract

The novel brominated flame retardant, 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), is an emerging environmental pollutant with undetermined toxicity. We investigated how BTBPE causes thyroid endocrine disruption with integrated in silico, in vitro, and in vivo assays. In yeast two-hybrid and T-Screen assays, BTBPE interacted with zebrafish thyroid hormone receptors with binding energies weaker than the TR agonist-3,3',5-Triiodo-l-thyronine (T3), and disrupted thyroid function as a thyroid receptor (TR) agonist. We examined the bioconcentration, developmental toxicity, and thyroid endocrine disruption in zebrafish after a 14-day exposure to BTBPE (1, 3, 10 μg/L). Thyroxine (T4) was lower in BTBPE-treated larvae, whereas corticotropin-releasing hormone (CRH) and thyroid-stimulating hormone (TSH) were higher. The gene transcription alterations along the hypothalamic-pituitary-thyroid (HPT) axis were observed. Furthermore, reduced locomotion suggested that BTBPE imparts developmental neurotoxicity at zebrafish early developmental stage. Establishing that BTBPE has thyroid endocrine-disrupting effects is an important step for understanding and managing BTBPE toxicity.

摘要

新型溴化阻燃剂1,2 - 双(2,4,6 - 三溴苯氧基)乙烷(BTBPE)是一种毒性未知的新兴环境污染物。我们通过整合计算机模拟、体外和体内试验，研究了BTBPE如何导致甲状腺内分泌紊乱。在酵母双杂交和T - 筛选试验中，BTBPE与斑马鱼甲状腺激素受体相互作用，其结合能比TR激动剂3,3',5 - 三碘 - L - 甲状腺原氨酸(T3)弱，并作为甲状腺受体(TR)激动剂破坏甲状腺功能。我们研究了斑马鱼在暴露于BTBPE(1、3、10μg/L)14天后的生物富集、发育毒性和甲状腺内分泌紊乱情况。经BTBPE处理的幼虫甲状腺素(T4)水平较低，而促肾上腺皮质激素释放激素(CRH)和促甲状腺激素(TSH)水平较高。观察到下丘脑 - 垂体 - 甲状腺(HPT)轴沿线的基因转录变化。此外，运动能力下降表明BTBPE在斑马鱼早期发育阶段具有发育神经毒性。确定BTBPE具有甲状腺内分泌干扰作用是理解和管理BTBPE毒性的重要一步。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51bd/11504562/8d190a2beed6/eh3c00140_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51bd/11504562/b58a970404b0/eh3c00140_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51bd/11504562/1eb3528b8e02/eh3c00140_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51bd/11504562/f312ebe1f27a/eh3c00140_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51bd/11504562/537b8249769c/eh3c00140_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51bd/11504562/8d190a2beed6/eh3c00140_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51bd/11504562/b58a970404b0/eh3c00140_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51bd/11504562/1eb3528b8e02/eh3c00140_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51bd/11504562/f312ebe1f27a/eh3c00140_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51bd/11504562/537b8249769c/eh3c00140_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51bd/11504562/8d190a2beed6/eh3c00140_0005.jpg

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