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Antimicrobial Triclocarban Exhibits Higher Agonistic Activity on Estrogen-Related Receptor γ than Triclosan at Human Exposure Levels: A Novel Estrogenic Disruption Mechanism
Environmental Science & Technology Letters ( IF 10.9 ) Pub Date : 2020-05-11 , DOI: 10.1021/acs.estlett.0c00338
Lin-Ying Cao 1 , Yun-Hao Xu 1 , Sen He 1 , Xiao-Min Ren 2 , Yuan Yang 1 , Shuang Luo 1 , Xian-De Xie 1 , Lin Luo 1
Affiliation  

Triclosan (TCS) and triclocarban (TCC) are two widely used antimicrobial agents that have been reported to be estrogenic disruptors. Previous researches have shown that TCC and TCS exhibit weak or no agonistic activity on classical estrogen receptors. We demonstrate first in the present study that TCS and TCC disrupt the estrogen system via the estrogen-related receptor γ (ERRγ) at human exposure levels. The fluorescence competitive binding assay showed that TCC had approximately 9-fold higher binding affinity with ERRγ than TCS. TCS and TCC demonstrated higher binding potency with ERRγ than a synthetic ERRγ agonist GSK4716, with a dissociation constant of 886 ± 141 and 96 ± 10 nM, respectively. By using the reporter gene assay, we found that TCS and TCC exerted agonistic activity toward ERRγ, with the lowest observed effective concentration of 100 and 10 nM, respectively. Molecular docking showed that TCS and TCC tended to present an ERRγ agonistic binding mode, and TCC exhibited lower binding energy than TCS, which provided a good theoretical explanation for our experimental observations. Our results revealed a novel mechanism for the estrogenic disruption of TCS and TCC, demonstrating that TCC deserves more attention in future research due to its higher activity.

中文翻译:

在人体暴露水平下,抗菌三氯卡班对雌激素相关受体γ的拮抗活性高于三氯生:一种新的雌激素破坏机制

三氯生(TCS)和三氯卡班(TCC)是两种广泛使用的抗菌剂,据报道它们是雌激素破坏剂。先前的研究表明,TCC和TCS对经典的雌激素受体表现出弱的或没有激动作用。我们在本研究中首先证明,TCS和TCC在人体暴露水平下会通过雌激素相关受体γ(ERRγ)破坏雌激素系统。荧光竞争结合试验表明,TCC与ERRγ的结合亲和力比TCS高约9倍。与合成的ERRγ激动剂GSK4716相比,TCS和TCC与ERRγ的结合力更高,解离常数分别为886±141和96±10 nM。通过使用报告基因检测,我们发现TCS和TCC对ERRγ具有激动作用,观察到的最低有效浓度分别为100和10 nM。分子对接表明,TCS和TCC趋向于呈现ERRγ激动结合模式,并且TCC的结合能低于TCS,这为我们的实验观察提供了良好的理论解释。我们的研究结果揭示了TCS和TCC雌激素破坏的新机制,表明TCC因其更高的活性而在未来的研究中值得更多关注。
更新日期:2020-05-11
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