Fluoride Exposure Induces Inhibition of Sodium/Iodide Symporter (NIS) Contributing to Impaired Iodine Absorption and Iodine Deficiency: Molecular Mechanisms of Inhibition and Implications for Public Health

Abstract

The sodium iodide symporter (NIS) is the plasma membrane glycoprotein that mediates active iodide transport in the thyroid and other tissues, such as the salivary, gastric mucosa, rectal mucosa, bronchial mucosa, placenta and mammary glands. In the thyroid, NIS mediates the uptake and accumulation of iodine and its activity is crucial for the development of the central nervous system and disease prevention. Since the discovery of NIS in 1996, research has further shown that NIS functionality and iodine transport is dependent on the activity of the sodium potassium activated adenosine 5′-triphosphatase pump (Na+, K+-ATPase). In this article, I review the molecular mechanisms by which F inhibits NIS expression and functionality which in turn contributes to impaired iodide absorption, diminished iodide-concentrating ability and iodine deficiency disorders. I discuss how NIS expression and activity is inhibited by thyroglobulin (Tg), tumour necrosis factor alpha (TNF-α), transforming growth factor beta 1 (TGF-β1), interleukin 6 (IL-6) and Interleukin 1 beta (IL-1β), interferon-γ (IFN-γ), insulin like growth factor 1 (IGF-1) and phosphoinositide 3-kinase (PI3K) and how fluoride upregulates expression and activity of these biomarkers. I further describe the crucial role of prolactin and megalin in regulation of NIS expression and iodine homeostasis and the effect of fluoride in down regulating prolactin and megalin expression. Among many other issues, I discuss the potential conflict between public health policies such as water fluoridation and its contribution to iodine deficiency, neurodevelopmental and pathological disorders. Further studies are warranted to examine these associations.

Genomic and Non-Genomic Mechanisms of Action of Thyroid Hormones and Their Catabolite 3,5-Diiodo-L-Thyronine in Mammals

“…In the case of iodine shortage, hypothyroidism follows. From this point of view, it is of note that fluoride is able to inhibit NIS functioning through different molecular mechanisms, such as inhibition of the Na + /K + -dependent ATPase, and upregulation of cytokines (including interleukins IL-6 and IL-1β, and TGFα), that in turn inhibit biosynthesis of NIS [43].…”

Interference on Iodine Uptake and Human Thyroid Function by Perchlorate-Contaminated Water and Food

“…Concerns over fluoride overexposure through drinking water have been raised in several countries [124], in which the levels of fluoride intake exceed safety limits, leading to a relevant increase in the prevalence of both dental and skeletal fluorosis [125]. Fluoride has been found to block I uptake by two fundamental mechanisms: inhibition of sodium-potassium ATPase and a cytokine-mediated reduction in NIS gene expression [126]. Indeed, fluoride exposure in early stages of life, mostly for preventing dental caries, is believed to be linked with an higher risk of future development of several diseases, including hypothyroidism and impaired intellective quotient [127].…”

A Schiff base colorimetric chemosensor for CN‐ ion and its dioxidomolybdenum (VI) complexes: Evaluation of structural aspects and optoelectronic properties

“…Anions show a decisive role in biology, specifically in the metabolism of all living organisms, medical field, environmental science, chemical and industrial processes . Nevertheless these anions are vital for living organisms, unnecessary accumulation of these anions in human body leads to the perpetual damaging effect to the various organs including kidney, bones, liver etc. Amongst the various anions, cyanide ion is the most fretful one since it plays a death‐defying role as a pollutant in environmental as well as biological field .…”