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 150 ppm in the drinking water. Real-time polymerase chain reaction was performed to analyze transforming growth factor beta 1 (TGF-?1) 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 150 ppm fluoride (compared to 0 ppm) for areas or number of cells that stained with Masson trichrome or with antibodies against collagen type I, alpha-smooth muscle actin (?-SMA, a myofibroblast marker), ED1, ED2, and ED3 (macrophage markers), and TGF-?1. 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-?1-fibroblast/myofibroblast-collagen synthesis pathway.
Dose-effect relationship between drinking water fluoride levels and damage to liver and kidney functions in children
Although a dose-effect relationship between water fluoride levels and damage to liver and kidney functions in animals has been reported, it was not demonstrated in humans. To evaluate the effects of drinking water fluoride levels on the liver and kidney functions in children with and without dental fluorosis, we identified
Bone disease in hemodialysis patients with particular reference to the effect of fluoride
Forty-one patients on our chronic hemodialysis program were assessed for the degree of progression of bone disease over an average period of 46 months. Seven patients were using a fluoridated dialysate. Four of these seven patients developed a marked increase in osteoid as judged by bone biopsy, while in the
Changes in fluoride levels in the liver, kidney, and brain and in neurotransmitters of mice after subacute administration of fluoride
The effects of fluoride after subacute oral administration of NaF at levels of 0, 1, 5, 25, and 125 ppm F– were evaluated in adult male BALB/c mice. Fluoride levels in the murine liver, kidney, and cerebrum after one month were determined using a highly sensitive flow-injection apparatus with a
Kidney function and structure in chronic fluorosis
An investigation has been carried out on the effects of the intake of small amounts of sodium fluoride on kidney structure and function in rats, with a view to the possibility of establishing some means of testing for the toxic effects of fluorine in human beings, and of demonstrating the
Prevention of bony fluorosis in aluminum smelter workers. A five-year study of fluoride absorption and excretion -- Pt. 3.
1. A study of over 52,000 urinary fluoride determinations collected over a 5-year period among aluminum smelter workers is described. The pre-shift urinary fluoride concentration (representative of bony burden) appears to increase less rapidly than the post-shift concentration. This slow rate of bony buildup of pre-shift urinary fluoride concentrations reflects
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