Stereoisomeric selectivity in the endocrine-disrupting potential of cypermethrin using in vitro, in vivo, and in silico assays

Quan Zhang; Shuqing Yu; Xiaoyang Chen; Lili Fu; Wei Dai; Sijia Gu

doi:10.1016/j.jhazmat.2021.125389

Stereoisomeric selectivity in the endocrine-disrupting potential of cypermethrin using in vitro, in vivo, and in silico assays

J Hazard Mater. 2021 Jul 15:414:125389. doi: 10.1016/j.jhazmat.2021.125389. Epub 2021 Feb 20.

Authors

Quan Zhang¹, Shuqing Yu², Xiaoyang Chen³, Lili Fu², Wei Dai², Sijia Gu²

Affiliations

¹ Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou, Zhejiang 310032, PR China. Electronic address: quanzhang@zjut.edu.cn.
² Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou, Zhejiang 310032, PR China.
³ Institute of Hydraulic and Environmental Engineering, Zhejiang University of Water Resources and Electric Power, Hangzhou, Zhejiang 310018, PR China.

PMID: 33677314
DOI: 10.1016/j.jhazmat.2021.125389

Abstract

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 RIC₂₀ of 9.1 × 10^-7, 7.6 × 10^-7, and 1.0 × 10^-6 M, respectively. β-CYP exhibited only ERα-mediated agonistic activity with a REC₂₀ of 2.1 × 10^-6 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.

Keywords: Cypermethrin; Endocrine-disrupting effects; Stereoisomeric selectivity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Endocrine Disruptors* / toxicity
Humans
Molecular Docking Simulation
Pyrethrins
Stereoisomerism
Zebrafish

Substances

Endocrine Disruptors
Pyrethrins
cypermethrin