Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou, Zhejiang 310032, PR China.
Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou, Zhejiang 310032, PR China.
J Hazard Mater. 2021 Jul 15;414:125389. doi: 10.1016/j.jhazmat.2021.125389. Epub 2021 Feb 20.
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 RIC of 9.1 × 10, 7.6 × 10, and 1.0 × 10 M, respectively. β-CYP exhibited only ERα-mediated agonistic activity with a REC of 2.1 × 10 M. 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 of 3-βHSD, indicating the block of turning cholesterol into different hormones. Both α-CYP and β-CYP upregulated genes encoding estrogen- and aldosterone-forming enzymes including 17-βHSD, CYP19, STAR, and CYP11B2. 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.
尽管拟除虫菊酯（CYP）立体异构体在环境生物群中无处不在，但 α-CYP、β-CYP 和 θ-CYP 的内分泌干扰效力的立体选择性尚未得到很好的研究。在这项研究中，采用双荧光素酶报告基因检测法，通过四个受体（ERα、GRα、MR 和 RXR）分析它们的潜在内分泌干扰作用。结果表明，α-CYP 对 ERα、GRα 和 MR 具有拮抗作用，RIC 分别为 9.1×10、7.6×10 和 1.0×10 M。β-CYP 仅表现出对 ERα 的激动活性，REC 为 2.1×10 M。CYP 立体异构体均不与 RXR 相互作用。分子对接表明，α-CYP 与化合物中 GRα 的结合能力最强。人肾上腺皮质癌细胞（H295R）中类固醇激素相关基因的表达水平显示，这三种化合物均抑制 3-βHSD 的转录，表明阻止胆固醇转化为不同的激素。α-CYP 和 β-CYP 均上调编码雌激素和醛固酮形成酶的基因，包括 17-βHSD、CYP19、STAR 和 CYP11B2。斑马鱼胚胎的死亡率和畸形毒性检测表明，毒性顺序为 α-CYP > β-CYP > θ-CYP。我们的结果表明，α-CYP 可能具有最强的内分泌干扰作用。这里提供的数据将有助于系统地了解拟除虫菊酯内分泌干扰作用中的立体选择性。
