PMID- 37086652 OWN - NLM STAT- MEDLINE DCOM- 20230515 LR - 20230515 IS - 1879-1514 (Electronic) IS - 0166-445X (Linking) VI - 259 DP - 2023 Jun TI - Thyroid endocrine disruption induced by [C(8)mim]Br: An integrated in vivo, in vitro, and in silico study. PG - 106535 LID - S0166-445X(23)00138-8 [pii] LID - 10.1016/j.aquatox.2023.106535 [doi] AB - Conventional thyroid-disrupting chemicals (TDCs) such as polybrominated diphenyl ethers, polychlorinated biphenyls, and bisphenols perturb animal's thyroid endocrine system by mimicking the action of endogenous thyroid hormones (THs), since they share a similar backbone structure of coupled benzene rings with THs. 1-methyl-3-octylimidazolium bromide ([C(8)mim]Br), a commonly used ionic liquid (IL), has no structural similarity to THs. Whether it interferes with thyroid function and how its mode of action differs from conventional TDCs is largely unknown. Herein, zebrafish embryo-larvae experiments (in vivo), GH3 cell line studies (in vitro), and molecular simulation analyses (in silico) were carried out to explore the effect of [C(8)mim]Br on thyroid homeostasis and its underlying mechanism. Molecular docking results suggested that [C(8)mim](+) likely bound to retinoid X receptors (RXRs), which may compromise the formation of TH receptor/RXR heterodimers. This then perturbed the negative regulation of thyroid-stimulating hormone beta (tshbeta) transcription by T3 in GH3 cell line. The resulting enhancement of tshbeta expression further caused hyperthyroidism and developmental toxicity in larval zebrafish. These findings provided a crucial aspect of the ecological risks of ILs, and presented a new insight into the thyroid-disrupting mechanisms for emerging pollutants that do not have structural similarity to THs. CI - Copyright (c) 2023. Published by Elsevier B.V. FAU - Wei, Penghao AU - Wei P AD - School of Environmental and Municipal Engineering, Qingdao University of Technology, Qingdao 266520, China; School of Environmental Science and Engineering, Shandong University, Qingdao 266237, China. FAU - Xiao, Yihua AU - Xiao Y AD - School of Environmental and Municipal Engineering, Qingdao University of Technology, Qingdao 266520, China. FAU - Liu, Changqing AU - Liu C AD - School of Environmental and Municipal Engineering, Qingdao University of Technology, Qingdao 266520, China. FAU - Yan, Bing AU - Yan B AD - Institute of Environmental Research at Greater Bay Area, Key Laboratory for Water Quality and Conservation of the Pearl River Delta, Ministry of Education, Guangzhou University, Guangzhou 510006, China. Electronic address: drbingyan@gzhu.edu.cn. LA - eng PT - Journal Article DEP - 20230407 PL - Netherlands TA - Aquat Toxicol JT - Aquatic toxicology (Amsterdam, Netherlands) JID - 8500246 RN - 0 (Water Pollutants, Chemical) RN - 0 (Thyroid Hormones) SB - IM MH - Animals MH - *Thyroid Gland MH - Zebrafish/metabolism MH - Molecular Docking Simulation MH - *Water Pollutants, Chemical/toxicity MH - Endocrine System MH - Thyroid Hormones/metabolism MH - Larva OTO - NOTNLM OT - Adverse outcome pathway OT - Ionic liquids OT - Retinoid X receptors OT - Thyroid endocrine system OT - Thyroid-stimulating hormone COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/04/23 00:41 MHDA- 2023/05/15 06:42 CRDT- 2023/04/22 18:07 PHST- 2023/03/05 00:00 [received] PHST- 2023/04/03 00:00 [revised] PHST- 2023/04/06 00:00 [accepted] PHST- 2023/05/15 06:42 [medline] PHST- 2023/04/23 00:41 [pubmed] PHST- 2023/04/22 18:07 [entrez] AID - S0166-445X(23)00138-8 [pii] AID - 10.1016/j.aquatox.2023.106535 [doi] PST - ppublish SO - Aquat Toxicol. 2023 Jun;259:106535. doi: 10.1016/j.aquatox.2023.106535. Epub 2023 Apr 7.