title: Permethrin is a potential thyroid-disrupting chemical: In vivo and in silico envidence.
abstract: Permethrin (PM), one of the most heavily used synthetic pyrethroids, has the potential to interfere with thyroid hormones in mammals, however, the effect is poorly recognized in aquatic organisms. Herein, embryonic zebrafish were exposed to PM (0, 1, 3 and 10μg/L) until 72h post-fertilization. We demonstrated that PM readily accumulated in larvae with a preference for cis-PM, inhibited development and increased thyroxine and 3,5,3'-triiodothyronine levels accompanying increase in the transcription of most target genes, i.e., thyroid-stimulating hormone β, deiodinases, thyroid receptors, involved in the hypothalamic-pituitary-thyroid axis. Further Western blot analysis indicated that transthyretin (TTR) protein was significantly increased. Molecular docking analysis and molecular dynamics simulations revealed that PM fits into three hydrophobic binding pocket of TTR, one of the molecular targets of thyroid hormone disrupting chemicals (THDCs), and forms strong van der Waals interactions with six resides of TTR, including Leu8, Leu 101, Leu125, Thr214, Leu218 and Val229, thus altering TTR activity. Both in vivo and in silico studies clearly disclosed that PM potentially disrupts the thyroid endocrine system in fish. This study provides a rapid and cost-effective approach for identifying THDCs and the underlying mechanisms.
authors.affiliation: Research Institute of Poyang Lake, Jiangxi Academy of Sciences, Nanchang 330029, China; College of Environment, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Wenqing
authors.initials: W
authors.lastname: Tu
authors.affiliation: College of Environment, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address: chaoxu@zjut.edu.cn.
authors.forename: Chao
authors.initials: C
authors.lastname: Xu
authors.affiliation: College of Environment, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Yuanxiang
authors.initials: Y
authors.lastname: Jin
authors.affiliation: College of Environment, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Lu
authors.affiliation: College of Environment, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Chunmian
authors.initials: C
authors.lastname: Lin
authors.affiliation: Research Institute of Poyang Lake, Jiangxi Academy of Sciences, Nanchang 330029, China.
authors.forename: Yongming
authors.initials: Y
authors.lastname: Wu
authors.affiliation: College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Liu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D052244:Endocrine Disruptors / Q000633:toxicity*; D004703:Endocrine System / Q000187:drug effects; D007453:Iodide Peroxidase / Q000378:metabolism; D007814:Larva / Q000187:drug effects; D062105:Molecular Docking Simulation; D026023:Permethrin / Q000737:chemistry / Q000633:toxicity*; D011722:Pyrethrins / Q000378:metabolism; D013961:Thyroid Gland / Q000187:drug effects*; D013963:Thyroid Hormones / Q000378:metabolism; D013972:Thyrotropin / Q000235:genetics; D013974:Thyroxine / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000737:chemistry / Q000633:toxicity*; D015027:Zebrafish / Q000196:embryology* / Q000254:growth & development
chemical_list: D052244:Endocrine Disruptors; D011722:Pyrethrins; D013963:Thyroid Hormones; D014874:Water Pollutants, Chemical; D014284:Triiodothyronine; D026023:Permethrin; D013972:Thyrotropin; D007453:Iodide Peroxidase; D013974:Thyroxine
keywords: Modeling; Permethrin; Thyroid hormone; Transthyretin; Zebrafish