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

Autor: Amadeu de Oliveira F; Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom.; Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil., MacVinish LJ; Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom., Amin S; Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom., Herath D; Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom., Jeggle P; Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom., Mela I; Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom., Pieri M; Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom., Sharma C; Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom., Jarvis GE; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom., Levy FM; Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil., Santesso MR; Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil., Khan ZN; Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil., Leite AL; Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil., Oliveira RC; Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil., Buzalaf MAR; Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil., Edwardson JM; Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom.
Jazyk: angličtina
Zdroj: Environmental toxicology [Environ Toxicol] 2018 Jan; Vol. 33 (1), pp. 63-71. Date of Electronic Publication: 2017 Oct 25.
DOI: 10.1002/tox.22495
Abstrakt: 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 IC 50 for fluoride of about 3 mM for both parameters. In the presence of 5 mM fluoride, transepithelial resistance fell exponentially with time, with a t 1/2 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.
(© 2017 Wiley Periodicals, Inc.)
Databáze: MEDLINE
Externí odkaz: