Stereoisomeric selectivity in the endocrine-disrupting potential of cypermethrin using in vitro, in vivo, and in silico assays.
Stereoisomeric selectivity in the endocrine-disrupting potential of cypermethrin using in vitro, in vivo, and in silico assays.
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使用体外、体内和计算机分析测定氯氰菊酯内分泌干扰潜力的立体异构选择性。
DOI：
10.1016/j.jhazmat.2021.125389
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发表时间：
2021-02
影响因子：
13.6
通讯作者：
Sijia Gu
中科院分区：
文献类型：
--
作者：
Quan Zhang;Shuqing Yu;Xiaoyang Chen;Lili Fu;Wei Dai;Sijia Gu
尽管氯氰菊酯立体异构体在环境生物中普遍存在，但α-氯氰菊酯、β-氯氰菊酯和θ-氯氰菊酯内分泌干扰效力的立体异构体选择性尚未得到很好的研究。本研究采用双荧光素酶报告基因分析法，通过ERα、GRα、MR和RXR四种受体分析其潜在的内分泌干扰作用。结果表明，α-雌二醇对ERα、GRα和MR具有拮抗作用，其RIC_（20）分别为9.1 × 10 - 7、7.6 × 10 - 7和1.0 × 10 - 6 M。β-雌二醇仅表现出ERα介导的激动活性，REC 20为2.1 × 10− 6 M。没有一种手性立体异构体与RXR相互作用。分子对接结果表明，α-环糊精与GRα的结合能力最强.人肾上腺皮质癌细胞（H295 R）中甾体激素相关基因的表达水平显示，3种化合物均能抑制3-βHSD的转录，阻断了胆固醇转化为不同激素的途径。α-雌二醇和β-雌二醇均能上调编码雌激素和醛固酮形成酶的基因，包括17-βHSD、CYP 19、STAR和CYP 11B 2。斑马鱼胚胎死亡和畸形毒性试验表明，α-β我们的研究结果表明，α-雌二醇可能具有最强的内分泌干扰作用。本文的研究结果将有助于系统地了解氯氰菊酯内分泌干扰效应的立体异构选择性。
Despite the ubiquity of cypermethrin (CYP) stereoisomers in environment biota, the stereoisomeric selectivity of endocrine-disrupting potency of α-CYP, β-CYP, and θ-CYP has not been well studied. In this study, dual-luciferase reporter gene assays were adopted to analyze their potential endocrine-disrupting effects via four receptors (ERα, GRα, MR and RXR). The results showed that α-CYP was antagonistic to ERα, GRα, and MR with RIC20of 9.1 × 10−7, 7.6 × 10−7, and 1.0 × 10−6M, respectively. β-CYP exhibited only ERα-mediated agonistic activity with a REC20of 2.1 × 10−6M. None of the CYP stereoisomers interacted with RXR. Molecular docking indicated that α-CYP had the strongest binding capacity to GRα among the compounds. The expression levels of steroid hormone-related genes in human adrenocortical carcinoma (H295R) cells displayed that all three compounds inhibited the transcription of3-βHSD,indicating the block of turning cholesterol into different hormones. Both α-CYP and β-CYP upregulated genes encoding estrogen- and aldosterone-forming enzymes including17-βHSD, CYP19, STAR,andCYP11B2. Mortality and malformation toxicity assays in zebrafish embryos revealed that the order of toxicity was α-CYP > β-CYP > θ-CYP. Our results indicated that α-CYP may pose the strongest endocrine-disrupting effects. The data provided here will be helpful to systematically understand stereoisomeric selectivity in the endocrine-disrupting effects of cypermethrin.
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影响因子：
6.9
作者：
Chao Xu;W. Tu;C. Lou;Yingying Hong;Mei-rong Zhao
通讯作者：
Chao Xu;W. Tu;C. Lou;Yingying Hong;Mei-rong Zhao
影响因子：
3.8
作者：
Sanderson, JT;Boerma, J;van den Berg, M
通讯作者：
van den Berg, M
DOI：
10.1016/j.cbpc.2020.108894
发表时间：
2020-09
期刊：
Comparative biochemistry and physiology. Toxicology & pharmacology : CBP
影响因子：
--
作者：
Juanli Lu;Qin Wu;Qing Yang;Guangyu Li;Ruiqi Wang;Yingxin Liu;Cunyu Duan;Shiyun Duan;Xuanyi He;Zhuo-yan Huang;Xitian Peng;Wei Yan;Jinhua Jiang
通讯作者：
Juanli Lu;Qin Wu;Qing Yang;Guangyu Li;Ruiqi Wang;Yingxin Liu;Cunyu Duan;Shiyun Duan;Xuanyi He;Zhuo-yan Huang;Xitian Peng;Wei Yan;Jinhua Jiang
影响因子：
11.4
作者：
Quan Zhang;Chang Yu;Lili Fu;Sijia Gu;Cui Wang
通讯作者：
Quan Zhang;Chang Yu;Lili Fu;Sijia Gu;Cui Wang
影响因子：
8.8
作者：
Julin Yuan;Jianlin Guo;Haiyang Wang;A. Guo;Qingping Lian;Z. Gu
通讯作者：
Julin Yuan;Jianlin Guo;Haiyang Wang;A. Guo;Qingping Lian;Z. Gu