000163894 001__ 163894
000163894 005__ 20251127152544.0
000163894 0247_ $$2doi$$a10.1016/j.tox.2014.01.012
000163894 0248_ $$2sideral$$a87370
000163894 037__ $$aART-2014-87370
000163894 041__ $$aeng
000163894 100__ $$aMartín-Pardillos, A.
000163894 245__ $$aEffect of water fluoridation on the development of medial vascular calcification in uremic rats
000163894 260__ $$c2014
000163894 5203_ $$aPublic 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 2 mM Pi for 5 days. Fluoride concentrations of 5–10 μM – 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 8.7 μM fluoride. In vivo, however, fluoridation of drinking water at 1.5 mg/L (concentration recommended by the WHO) and 15 mg/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.
000163894 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B008-09$$9info:eu-repo/grantAgreement/ES/MINECO/MAT2011-259911$$9info:eu-repo/grantAgreement/ES/MINECO/SAF2012-33898
000163894 540__ $$9info:eu-repo/semantics/closedAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000163894 590__ $$a3.621$$b2014
000163894 591__ $$aTOXICOLOGY$$b16 / 88 = 0.182$$c2014$$dQ1$$eT1
000163894 591__ $$aPHARMACOLOGY & PHARMACY$$b56 / 255 = 0.22$$c2014$$dQ1$$eT1
000163894 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000163894 700__ $$0(orcid)0000-0003-2907-0427$$aSosa, C.$$uUniversidad de Zaragoza
000163894 700__ $$0(orcid)0000-0003-0828-3212$$aMillán, A.$$uUniversidad de Zaragoza
000163894 700__ $$0(orcid)0000-0003-3457-323X$$aSorribas, V.$$uUniversidad de Zaragoza
000163894 7102_ $$11000$$2807$$aUniversidad de Zaragoza$$bDpto. Anat.Pat.Med.Leg.For.To.$$cArea Toxicología
000163894 7102_ $$12003$$2395$$aUniversidad de Zaragoza$$bDpto. Física Materia Condensa.$$cÁrea Física Materia Condensada
000163894 773__ $$g318 (2014), 40-50$$pToxicology$$tTOXICOLOGY$$x0300-483X
000163894 8564_ $$s452557$$uhttps://zaguan.unizar.es/record/163894/files/texto_completo.pdf$$yVersión publicada
000163894 8564_ $$s977061$$uhttps://zaguan.unizar.es/record/163894/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000163894 909CO $$ooai:zaguan.unizar.es:163894$$particulos$$pdriver
000163894 951__ $$a2025-11-27-15:23:38
000163894 980__ $$aARTICLE