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Title

Effect of water fluoridation on the development of medial vascular calcification in uremic rats

AuthorsMartín-Pardillos, Ana; Sosa, Cecilia; Millán, Ángel; Sorribas, Víctor
KeywordsVSMC (vascular smooth muscle cells)
MVC (medial vascular calcification)
CPD (calcium phosphate deposition)
CKD (chronic kidney disease)
Issue Date2014
PublisherElsevier
CitationToxicology 318: 40-50 (2014)
AbstractPublic water fluoridation is a common policy for improving dental health. Fluoride replaces the hydroxyls of hydroxyapatite, thereby improving the strength of tooth enamel, but this process can also occur in other active calcifications. This paper studies the effects of water fluoridation during the course of vascular calcification in renal disease.The effect of fluoride was studied in vitro and in vivo. Rat aortic smooth muscle cells were calcified with 2mM Pi for 5 days. Fluoride concentrations of 5-10μM - similar to those found in people who drink fluoridated water - partially prevented calcification, death, and osteogene expression in vitro. The anticalcifying mechanism was independent of cell activity, matrix Gla protein, and fetuin A expressions, and it exhibited an IC50 of 8.7μM fluoride. In vivo, however, fluoridation of drinking water at 1.5mg/L (concentration recommended by the WHO) and 15mg/L dramatically increased the incipient aortic calcification observed in rats with experimental chronic kidney disease (CKD, 5/6-nephrectomy), fed a Pi-rich fodder (1.2% Pi). Fluoride further declined the remaining renal function of the CKD animals, an effect that most likely overwhelmed the positive effect of fluoride on calcification in vitro. Ultrastructural analysis revealed that fluoride did not modify the Ca/P atomic ratio, but it was incorporated into the lattice of in vivo deposits. Fluoride also converted the crystallization pattern from plate to rode-like structures.In conclusion, while fluoride prevents calcification in vitro, the WHO's recommended concentrations in drinking water become nephrotoxic to CKD rats, thereby aggravating renal disease and making media vascular calcification significant. © 2014 Elsevier Ireland Ltd.
URIhttp://hdl.handle.net/10261/118290
DOI10.1016/j.tox.2014.01.012
Identifiersdoi: 10.1016/j.tox.2014.01.012
issn: 0300-483X
e-issn: 1879-3185
Appears in Collections:(ICMA) Artículos
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