title: The effects and underlying mechanism of excessive iodide on excessive fluoride-induced thyroid cytotoxicity.
abstract: In many regions, excessive fluoride and excessive iodide coexist in groundwater, which may lead to biphasic hazards to human thyroid. To explore fluoride-induced thyroid cytotoxicity and the mechanism underlying the effects of excessive iodide on fluoride-induced cytotoxicity, a thyroid cell line (Nthy-ori 3-1) was exposed to excessive fluoride and/or excessive iodide. Cell viability, lactate dehydrogenase (LDH) leakage, reactive oxygen species (ROS) formation, apoptosis, and the expression levels of inositol-requiring enzyme 1 (IRE1) pathway-related molecules were detected. Fluoride and/or iodide decreased cell viability and increased LDH leakage and apoptosis. ROS, the expression levels of glucose-regulated protein 78 (GRP78), IRE1, C/EBP homologous protein (CHOP), and spliced X-box-binding protein-1 (sXBP-1) were enhanced by fluoride or the combination of the two elements. Collectively, excessive fluoride and excessive iodide have detrimental influences on human thyroid cells. Furthermore, an antagonistic interaction between fluoride and excessive iodide exists, and cytotoxicity may be related to IRE1 pathway-induced apoptosis.
authors.affiliation: Tianjin Centers for Disease Control and Prevention, 6 Huayue Road, Hedong District, Tianjin 300011, PR China; School of Public Health, Tianjin Medical University, 22 Qi Xiang Tai Road, Heping District, Tianjin 300070, PR China. Electronic address: liuhongliang@cdctj.gov.cn.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Liu
authors.affiliation: Tianjin Centers for Disease Control and Prevention, 6 Huayue Road, Hedong District, Tianjin 300011, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zeng
authors.affiliation: Tianjin Centers for Disease Control and Prevention, 6 Huayue Road, Hedong District, Tianjin 300011, PR China.
authors.forename: Yushan
authors.initials: Y
authors.lastname: Cui
authors.affiliation: School of Public Health, Tianjin Medical University, 22 Qi Xiang Tai Road, Heping District, Tianjin 300070, PR China.
authors.forename: Linyu
authors.initials: L
authors.lastname: Yu
authors.affiliation: Tianjin Centers for Disease Control and Prevention, 6 Huayue Road, Hedong District, Tianjin 300011, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Tianjin Centers for Disease Control and Prevention, 6 Huayue Road, Hedong District, Tianjin 300011, PR China.
authors.forename: Changchun
authors.initials: C
authors.lastname: Hou
authors.affiliation: Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Hubei, Wuhan 430030, PR China.
authors.forename: Shun
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Tianjin Centers for Disease Control and Prevention, 6 Huayue Road, Hedong District, Tianjin 300011, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Tianjin Centers for Disease Control and Prevention, 6 Huayue Road, Hedong District, Tianjin 300011, PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Fu
authors.affiliation: School of Public Health, Tianjin Medical University, 22 Qi Xiang Tai Road, Heping District, Tianjin 300070, PR China.
authors.forename: Yeming
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Hubei, Wuhan 430030, PR China.
authors.forename: Chunyang
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Hubei, Wuhan 430030, PR China.
authors.forename: Xuemin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Hubei, Wuhan 430030, PR China. Electronic address: wangaiguo@mails.tjmu.edu.cn.
authors.forename: Aiguo
authors.initials: A
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics; D000091342:Endoplasmic Reticulum Chaperone BiP; D004722:Endoribonucleases / Q000235:genetics; D006360:Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D011193:Potassium Iodide / Q000633:toxicity*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D000071701:Regulatory Factor X Transcription Factors; D012969:Sodium Fluoride / Q000633:toxicity*; D013961:Thyroid Gland / Q000166:cytology*; D051742:Transcription Factor CHOP / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: C497249:DDIT3 protein, human; D004268:DNA-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D017382:Reactive Oxygen Species; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D014874:Water Pollutants, Chemical; D051742:Transcription Factor CHOP; D011193:Potassium Iodide; D012969:Sodium Fluoride; C528229:ERN1 protein, human; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases
keywords: Apoptosis; Cytotoxicity; Fluoride; IRE1; Iodide; Thyroid