Enteric innervation combined with proteomics for the evaluation of the effects of chronic fluoride exposure on the duodenum of rats

Melo, Carina Guimarães de Souza; Perles, Juliana Vanessa Colombo Martins; Zanoni, Jacqueline Nelisis; Souza, Sara Raquel Garcia de; Santos, Erika Xavier; Leite, Aline de Lima; Heubel, Alessandro Domingues; Souza, Camila Oliveira e; Souza, Juliana; Buzalaf, Marília Afonso Rabelo

doi:10.1038/s41598-017-01090-y

Cited by 28 publications

(28 citation statements)

References 76 publications

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“…The fluoride exposure doses used in our study (10 and 50 mg/L) are often employed [ 32 – 34 ] and lead to a plasma fluoride levels in rodents similar to the ones found in humans consuming artificially fluoridated water or living in areas of endemic fluorosis, respectively [ 35 ]. It is important to note that F metabolism in rodents is 5–10 times faster than that in humans and the concentrations used in this investigation, 10 and 50 mg/L, correspond to 1-2 and 5–10 mg/L, respectively, for humans in the drinking water [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Chronic Exposure to Sodium Fluoride Triggers Oxidative Biochemistry Misbalance in Mice: Effects on Peripheral Blood Circulation

Miranda

Gomes

Bittencourt

et al. 2018

Oxidative Medicine and Cellular Longevity

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The excessive fluoride (F) exposure is associated with damage to cellular processes of different tissue types, due to changes in enzymatic metabolism and breakdown of redox balance. However, few studies evaluate doses of F compatible with human consumption. Thus, this study evaluated the effects of chronic exposure to sodium fluoride (NaF) on peripheral blood of mice from the evaluation of biochemical parameters. The animals were divided into three groups (n = 10) and received three concentrations of NaF in the drinking water for 60 days: 0 mg/L F, 10 mg/L F, and 50 mg/L F. The blood was then collected for trolox equivalent antioxidant capacity (TEAC), thiobarbituric acid reactive substances (TBARS), concentrations of nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH). The results showed that doses of 10 mg/L F and 50 mg/L F were able to increase TBARS concentration and decrease NO levels and CAT activity in the blood, but there was no statistical difference for SOD levels. The 50 mg/L F group showed an increase in TEAC levels and a decrease in the GSH content when compared to the control group. In this way, oxidative changes in blood from chronic exposure to F, especially at the highest dose, indicate that F may be a toxic agent and, therefore, the long-term exposure to excessive doses should be avoided.

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Section: Discussionmentioning

confidence: 99%

Chronic Exposure to Sodium Fluoride Triggers Oxidative Biochemistry Misbalance in Mice: Effects on Peripheral Blood Circulation

Miranda

Gomes

Bittencourt

et al. 2018

Oxidative Medicine and Cellular Longevity

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“…Hence, the Caco‐2 cell monolayers are considerably less sensitive to fluoride than M‐1 mouse kidney cortical collecting duct epithelia, in which both I sc and R t are reduced to zero at 1 mM fluoride (IC 50 , 300 μM). Although its molecular basis is unclear and the first insights into this aspect have only been recently reported, this difference might reflect the fact that the intestinal epithelium is the first barrier encountered by ingested fluoride.…”

Section: Discussionmentioning

confidence: 99%

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

Oliveira

MacVinish

Amin

et al. 2017

Environmental Toxicology

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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.

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“…Optimal water fluoridation is not associated with other harmful effects besides dental fluorosis [ 6 ]. On the other hand, higher concentrations might also affect bone [ 7 ], liver [ 8 ], kidney [ 9 , 10 ], and gut [ 11 , 12 ]. In addition, studies have suggested that ingesting high doses of fluoride during childhood may influence on intellectual abilities and cognitive development [ 13 , 14 , 15 , 16 ], although there are no reports of harmful effects on humans exposed to therapeutic doses [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of Fluoride Long-Term Exposure over the Cerebellum: Global Proteomic Profile, Oxidative Biochemistry, Cell Density, and Motor Behavior Evaluation

Lopes

Ferreira

Davis

et al. 2020

IJMS

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Although the literature does not provide evidence of health risks from exposure to fluoride (F) in therapeutic doses, questions remain about the effects of long-term and high-dose use on the function of the central nervous system. The objective of this study was to investigate the effect of long-term exposure to F at levels similar to those found in areas of artificial water fluoridation and in areas of endemic fluorosis on biochemical, proteomic, cell density, and functional parameters associated with the cerebellum. For this, mice were exposed to water containing 10 mg F/L or 50 mg F/L (as sodium fluoride) for 60 days. After the exposure period, the animals were submitted to motor tests and the cerebellum was evaluated for fluoride levels, antioxidant capacity against peroxyl radicals (ACAP), lipid peroxidation (MDA), and nitrite levels (NO). The proteomic profile and morphological integrity were also evaluated. The results showed that the 10 mg F/L dose was able to decrease the ACAP levels, and the animals exposed to 50 mg F/L presented lower levels of ACAP and higher levels of MDA and NO. The cerebellar proteomic profile in both groups was modulated, highlighting proteins related to the antioxidant system, energy production, and cell death, however no neuronal density change in cerebellum was observed. Functionally, the horizontal exploratory activity of both exposed groups was impaired, while only the 50 mg F/L group showed significant changes in postural stability. No motor coordination and balance impairments were observed in both groups. Our results suggest that fluoride may impair the cerebellar oxidative biochemistry, which is associated with the proteomic modulation and, although no morphological impairment was observed, only the highest concentration of fluoride was able to impair some cerebellar motor functions.

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Enteric innervation combined with proteomics for the evaluation of the effects of chronic fluoride exposure on the duodenum of rats

Cited by 28 publications

References 76 publications

Chronic Exposure to Sodium Fluoride Triggers Oxidative Biochemistry Misbalance in Mice: Effects on Peripheral Blood Circulation

Chronic Exposure to Sodium Fluoride Triggers Oxidative Biochemistry Misbalance in Mice: Effects on Peripheral Blood Circulation

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

Effects of Fluoride Long-Term Exposure over the Cerebellum: Global Proteomic Profile, Oxidative Biochemistry, Cell Density, and Motor Behavior Evaluation

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