title: Endocrine disrupting potential of fipronil and its metabolite in reporter gene assays.
abstract: There is a rising concern about the ecological safety and potential health risks caused by pesticides that are commonly present in the environment. Previous studies have shown that metabolites of pesticides sometimes possess more potent endocrine activity than the parent compounds. However very little efforts had been devoted to evaluate the environmental risks of pesticide metabolites. In the present study, we evaluated the agonistic and antagonistic activities of fipronil and its metabolite, fipronil sulfone, and compared by in vitro reporter gene assays using CHO-K1 cells. For estrogenic and antiestrogenic activities, both fipronil and fipronil sulfone showed no agonistic activities but exhibited the similarly antagonistic activities via estrogen receptor α (ERα), with the RIC20 of 6.4 × 10(-7)M and 9.8 × 10(-7)M, respectively. In the thyroid hormone receptor (TR) assay, only fipronil sulfone showed anti-thyroid hormone activity with the RIC20 of 8.2 × 10(-7)M. Furthermore, molecular docking was employed to support the results in TR assay with lower MolDock score for fipronil sulfone. Data provided here suggested that it is of great significance to study the endocrine-disrupting effects of pesticide's metabolites, especially those with persistence in environment and high toxicity to non-targeted organisms.
authors.affiliation: College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Meiya
authors.initials: M
authors.lastname: Lu
authors.affiliation: College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Du
authors.affiliation: College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Peixue
authors.initials: P
authors.lastname: Zhou
authors.affiliation: College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, 401 Park Drive, Landmark Center West, Boston, MA 02215, United States.
authors.forename: Chensheng
authors.initials: C
authors.lastname: Lu
authors.affiliation: College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address: quanzhang@zjut.edu.cn.
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D016466:CHO Cells; D003412:Cricetulus; D052244:Endocrine Disruptors / Q000633:toxicity*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D017930:Genes, Reporter; D007306:Insecticides / Q000633:toxicity*; D062105:Molecular Docking Simulation; D011720:Pyrazoles / Q000633:toxicity*; D037042:Thyroid Hormone Receptors beta / Q000378:metabolism*
chemical_list: D052244:Endocrine Disruptors; D047628:Estrogen Receptor alpha; D007306:Insecticides; D011720:Pyrazoles; D037042:Thyroid Hormone Receptors beta; C534368:fipronil sulfone; C082360:fipronil
keywords: Estrogen; Fipronil; Metabolite; Molecular docking; Thyroid hormone