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Fluoride potentiates tubulointerstitial nephropathy caused by unilateral ureteral obstruction.
- Source :
-
Toxicology [Toxicology] 2017 Dec 01; Vol. 392, pp. 106-118. Date of Electronic Publication: 2017 Oct 09. - Publication Year :
- 2017
-
Abstract
- The contamination of ground water by fluoride has been reported worldwide. Most fluoride (approximately 70%) is filtered by the kidneys; humans or experimental animals with renal damage therefore may be more affected by fluoride exposure than those with normal kidney function. Tubulointerstitial fibrosis, which involves macrophage-promoted extracellular matrix production and myofibroblast migration, can be induced in rats by unilateral ureteral obstruction (UUO). We examined the effects of fluoride exposure on tubulointerstitial fibrosis in the obstructed kidney of UUO rats. The left ureters of 6-week-old male rats were ligated using silk sutures. Fluoride was then administered for 2 weeks at doses of 0, 75, and 150ppm in the drinking water. Real-time polymerase chain reaction was performed to analyze transforming growth factor beta 1 (TGF-β <subscript>1</subscript> ) transcription; histological and immunohistochemical staining were used to identify positive areas within the renal cortex and staining-positive cells by image analysis. Significant increases were observed in the obstructed kidneys of UUO rats exposed to 150ppm fluoride (compared to 0ppm) for areas or number of cells that stained with Masson trichrome or with antibodies against collagen type I, alpha-smooth muscle actin (α-SMA, a myofibroblast marker), ED1, ED2, and ED3 (macrophage markers), and TGF-β <subscript>1</subscript> . Taken together, these observations suggested that fluoride exacerbates tuburointerstitial nephropathy resulting from UUO, and that this effect occurs via activation of the M2 macrophage-TGF-β1-fibroblast/myofibroblast-collagen synthesis pathway.<br /> (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Subjects :
- Actins genetics
Actins metabolism
Animals
Dose-Response Relationship, Drug
Fluorides blood
Kidney drug effects
Kidney physiopathology
Macrophages cytology
Macrophages drug effects
Male
Myofibroblasts cytology
Myofibroblasts drug effects
Organ Size drug effects
Rats
Rats, Sprague-Dawley
Transforming Growth Factor beta1 genetics
Transforming Growth Factor beta1 metabolism
Fluorides toxicity
Kidney Diseases pathology
Ureteral Obstruction pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-3185
- Volume :
- 392
- Database :
- MEDLINE
- Journal :
- Toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 29024711
- Full Text :
- https://doi.org/10.1016/j.tox.2017.10.003