Role of endoplasmic reticulum stress-induced apoptosis in rat thyroid toxicity caused by excess fluoride and/or iodide

Environ Toxicol Pharmacol. 2016 Sep:46:277-285. doi: 10.1016/j.etap.2016.08.007. Epub 2016 Aug 9.

Abstract

Excess fluoride and iodide coexist in drinking water in many regions, but few studies have investigated the single or interactive effects on thyroid in vivo. In our study, Wistar rats were exposed to excess fluoride and/or iodide through drinking water for 2 or 8 months. The structure and function of the thyroid, cells apoptosis and the expression of inositol-requiring enzyme 1 (IRE1) pathway-related factors were analyzed. Results demonstrated that excess fluoride and/or iodide could change thyroid follicular morphology and alter thyroid hormone levels in rats. After 8 months treatment, both single and co-exposure of the two microelements could raise the thyroid cells apoptosis. However, the expressions of IRE1-related factors were only increased in fluoride-alone and the combined groups. In conclusion, thyroid structure and thyroid function were both affected by excess fluoride and/or iodide. IRE1-induced apoptosis were involved in this cytotoxic process caused by fluoride or the combination of two microelements.

Keywords: Endoplasmic reticulum stress; Fluoride; Iodide; Rat; Thyroid.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Drug Synergism
  • Endoplasmic Reticulum Stress / drug effects*
  • Iodates / administration & dosage
  • Iodates / toxicity*
  • Membrane Proteins / metabolism
  • Potassium Compounds / administration & dosage
  • Potassium Compounds / toxicity*
  • Protein Serine-Threonine Kinases / metabolism
  • Rats, Wistar
  • Sodium Fluoride / administration & dosage
  • Sodium Fluoride / toxicity*
  • Thyroid Function Tests
  • Thyroid Gland / drug effects*
  • Thyroid Gland / metabolism
  • Thyroid Gland / pathology

Substances

  • Iodates
  • Membrane Proteins
  • Potassium Compounds
  • Sodium Fluoride
  • Ern2 protein, rat
  • Protein Serine-Threonine Kinases
  • potassium iodate