The effect of fluoride on the structure, function, and proteome of intestinal epithelia

Fluoride exposure is widespread, with drinking water commonly containing natural and artificially added sources of the ion. Ingested fluoride undergoes absorption across the gastric and intestinal epithelia. Previous studies have reported adverse gastrointestinal effects with high levels of fluoride...

Full description

Saved in:

Bibliographic Details
Published in:	Environmental toxicology Vol. 33; no. 1; pp. 63 - 71
Main Authors:	Amadeu de Oliveira, Flávia, MacVinish, Lesley J., Amin, Simran, Herath, Duleni, Jeggle, Pia, Mela, Ioanna, Pieri, Maria, Sharma, Chetanya, Jarvis, Gavin E., Levy, Flávia M., Santesso, Mariana R., Khan, Zohaib N., Leite, Aline L., Oliveira, Rodrigo C., Buzalaf, Marília A. R., Edwardson, J. Michael
Format:	Journal Article
Language:	English
Published:	United States Wiley Subscription Services, Inc 01-01-2018
Subjects:	Abnormalities Animals atomic force microscopy Caco-2 Cells Cell adhesion Cell Adhesion - drug effects cell stiffness Chlorides Chlorides - metabolism Drinking water Elastic Modulus - drug effects Electron microscopy epithelial ion transport Epithelium Exposure fluoride Fluorides Fluorides - pharmacology Forskolin gastrointestinal epithelia Humans Imaging techniques Immunofluorescence Intestinal Mucosa - drug effects Intestinal Mucosa - physiology Intestine Ion transport Large intestine Malformations Mechanical properties Mice Microscopy, Atomic Force Microscopy, Electron, Scanning Microscopy, Fluorescence Modulus of elasticity Monolayers Monomolecular films Patch-Clamp Techniques Proteins Proteome - drug effects Proteome - metabolism proteomics Rats Scanning electron microscopy Secretion Small intestine Structure-function relationships fluoride cell stiffness proteomics atomic force microscopy epithelial ion transport gastrointestinal epithelia
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Fluoride exposure is widespread, with drinking water commonly containing natural and artificially added sources of the ion. Ingested fluoride undergoes absorption across the gastric and intestinal epithelia. Previous studies have reported adverse gastrointestinal effects with high levels of fluoride exposure. Here, we examined the effects of fluoride on the transepithelial ion transport and resistance of three intestinal epithelia. We used the Caco‐2 cell line as a model of human intestinal epithelium, and rat and mouse colonic epithelia for purposes of comparison. Fluoride caused a concentration‐dependent decline in forskolin‐induced Cl– secretion and transepithelial resistance of Caco‐2 cell monolayers, with an IC50 for fluoride of about 3 mM for both parameters. In the presence of 5 mM fluoride, transepithelial resistance fell exponentially with time, with a t1/2 of about 7 hours. Subsequent imaging by immunofluorescence and scanning electron microscopy showed structural abnormalities in Caco‐2 cell monolayers exposed to fluoride. The Young's modulus of the epithelium was not affected by fluoride, although proteomic analysis revealed changes in expression of a number of proteins, particularly those involved in cell–cell adhesion. In line with its effects on Caco‐2 cell monolayers, fluoride, at 5 mM, also had profound effects on Cl– secretion and transepithelial resistance of both rat and mouse colonic epithelia. Our results show that treatment with fluoride has major effects on the structure, function, and proteome of intestinal epithelia, but only at concentrations considerably higher than those likely to be encountered in vivo, when much lower fluoride doses are normally ingested on a chronic basis.
Bibliography:	Funding information Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Grant/Award number: 88887.059581/2014‐00; Kidney Research UK, Grant/Award number: RP17/2012
ISSN:	1520-4081 1522-7278
DOI:	10.1002/tox.22495