The effects and underlying mechanism of excessive iodide on excessive fluoride-induced thyroid cytotoxicity

Environ Toxicol Pharmacol. 2014 Jul;38(1):332-40. doi: 10.1016/j.etap.2014.06.008. Epub 2014 Jun 27.


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.

Keywords: Apoptosis; Cytotoxicity; Fluoride; IRE1; Iodide; Thyroid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • DNA-Binding Proteins / genetics
  • Endoplasmic Reticulum Chaperone BiP
  • Endoribonucleases / genetics
  • Heat-Shock Proteins / genetics
  • Humans
  • Potassium Iodide / toxicity*
  • Protein Serine-Threonine Kinases / genetics
  • Reactive Oxygen Species / metabolism
  • Regulatory Factor X Transcription Factors
  • Sodium Fluoride / toxicity*
  • Thyroid Gland / cytology*
  • Transcription Factor CHOP / genetics
  • Transcription Factors / genetics
  • Water Pollutants, Chemical / toxicity*


  • DDIT3 protein, human
  • DNA-Binding Proteins
  • Endoplasmic Reticulum Chaperone BiP
  • HSPA5 protein, human
  • Heat-Shock Proteins
  • Reactive Oxygen Species
  • Regulatory Factor X Transcription Factors
  • Transcription Factors
  • Water Pollutants, Chemical
  • Transcription Factor CHOP
  • Potassium Iodide
  • Sodium Fluoride
  • ERN1 protein, human
  • Protein Serine-Threonine Kinases
  • Endoribonucleases