The effect of fluoride on the structure, function, and proteome of a renal epithelial cell monolayer

Antonio, Ligia Subitoni; Jeggle, Pia; MacVinish, Lesley J.; Bartram, James; Miller, Henry I.; Jarvis, Gavin E.; Levy, Flávia Mauad; Santesso, Mariana R.; Leite, Aline L.; Oliveira, Rodrigo Cardoso de; Buzalaf, Marília Afonso Rabelo; Edwardson, J. Michael

doi:10.1002/tox.22338

Cited by 13 publications

(5 citation statements)

References 40 publications

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“…The values of Young's modulus for control and fluoride‐treated cells were 12.9 ± 3.3 ( n = 4) and 21.0 ± 3.1; ( n = 4) kPa, respectively ( P = .12). Hence, fluoride treatment did not significantly affect the Young's modulus of the cells, as we reported recently for M‐1 mouse kidney cortical collecting duct epithelia . It is noteworthy that the Young's modulus of the Caco‐2 cell monolayer is substantially greater than the 1 kPa obtained for M‐1 cell monolayers, although it is similar to the value of about 25 kPa reported for MDCK cell monolayers …”

Section: Resultssupporting

confidence: 84%

“…In our experiments, fluoride reduced forskolin‐stimulated I sc and R t over identical concentration ranges (IC 50 , 3.1 mM). 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: 98%

“…The fraction containing hydrophobic proteins was collected and the proteins were purified using detergent removal spin columns (Thermo Scientific). Proteins were extracted, reduced, alkylated, and digested as previously described, and then analyzed using a nanoAcquity UPLC‐XEVO QToF mass spectrometry system . Differences in expression between the groups were assessed using PLGS software and expressed as P < .05 for down‐regulated and (1 – P ) > 0.05 for up‐regulated proteins.…”

Section: Methodsmentioning

confidence: 99%

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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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Section: Resultssupporting

confidence: 84%

Section: Discussionmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

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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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“…In a recent study, the morphological alterations such as degeneration, necrosis of the tubular cells, renal tubular hyaline casts and swollen glomeruli abnormalities were detected in 12, 24, 48 mg/kg body weight NaF exposure mice after 42 days [27]. Interestingly, a previous study reported that, NaF could reduce the integrity of tight connections in M-1 cell monolayers of mice [28]. The impact of SO 2 changed the ultra-structural lesions in renal proximal tubular lining cells [22].…”

Section: Discussionmentioning

confidence: 99%

Combination of Fluoride and SO2 Induce DNA Damage and Morphological Alterations in Male Rat Kidney

Gao

Liang

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: We investigated the combined toxic effect of sodium fluoride (NaF) and sulfur dioxide (SO₂) on kidney morphological changes and DNA damage in male Wistar rats. Methods: In this study we selected totally 96 male Wistar rats (12-week-old) then randomly group-housed them into four cages, treated with deionized water, NaF, SO₂ and co-treatment of NaF and SO₂ respectively. Morphological changes of kidney were detected by hematoxylin and eosin (H&E) staining at 2, 4, 6 and 8 weeks. Correspondingly, tailing ratio and comet length were measured by BAB Bs Comet Assay System, including DNA damage special unit were calculated to evaluate the grades of kidney DNA damage at the same time. Results: Treated groups showed a body weight decrease when compared to control group. However, no significant difference in the relative weight of kidney was found in all four groups. It is noteworthy that at 2, 4, 6 and 8 weeks after exposure, the morphological alteration of renal tubules were observed in all treated groups, especially in group-IV. Also, at 4 and 6 weeks, notable DNA damage was found in all treated groups, as assessed by significantly increasing trend of comet length tailing ratio. Conclusion: The study manifests that presence of NaF and SO₂ will not only induce renal tissue lesions but also impact DNA integrity. In addition, this combined exposure exhibits a synergistic effect, characterizing a dose-dependence and time correlation. These findings may provide novel insights regarding perturbations of DNA damage and its functions as a potential new mechanism, by which cautious interpretation of NaF and SO₂ co-exposure evolved in both animals and human beings is necessary.

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“…As we all know that F is necessary in lots of physiological activities. However, previous literatures have demonstrated that over-consumption of F not only damaged hard tissues, such as bone [3,4] and tooth [5,6], but also soft tissues, such as liver, kidney, thyroid, testis, uterus, and ovary [7][8][9][10][11]. Recently, literatures have suggested that over-intake F had intestinal toxicity [12,13], while the underlying mechanisms of the intestinal toxicity of F are unclear.…”

Section: Introductionmentioning

confidence: 99%

Dietary High Sodium Fluoride Impairs Digestion and Absorption Ability, Mucosal Immunity, and Alters Cecum Microbial Community of Laying Hens

Miao

Zhu

et al. 2020

Animals

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(1) Background: This study was conducted to investigate the effects of dietary fluoride (F) on tissue retention, digestive enzymes activities, mucosal immunity, and cecum microbial community of laying hens. (2) Methods: Total of 288 37-week-old Hy-Line Gray laying hens with similar laying rate (85.16% ± 3.87%) were adapted to the basal diets for ten days, and then allocated into three groups at random (n = 9, 6, 6 replicates/group). The concentrations of F in the diets were 31.19 (the control group, CON), 431.38 (F400, low-F group) and 1237.16 mg/kg (F1200, high-F group), respectively. The trial lasted for 59 days. (3) Results: Results suggested that F residuals in duodenum responded to dietary F concentrations positively. The activities of amylase, maltase and lactase were decreased in high-F group, compared with those in the control group. The mRNA expression levels of jejunum and ileum secretory immunoglobulin A (sIgA) and Mucin 2, and sIgA concentrations were decreased inhigh-F group, than those in the control group. The observed operational taxonomic units (OTUs) of laying hens in high-F group were higher than the CON and low-F groups, and the bacterial structure was different from the other two groups. The Lactobacillus was higher in the control group, while Gammaproteobacteria, Escherichia-Shigella, Streptococcaceae, and Enterobacteriaceae were higher in the high-F group. (4) Conclusions: The actual results confirmed that dietary high F intake increased the F residuals in duodenum, and reduced the digestion and absorption of nutrients and immunity via decreasing the activities of digestive enzymes, impairing intestine mucosal immunity, and disturbing the cecum microbial homeostasis of laying hens.

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The effect of fluoride on the structure, function, and proteome of a renal epithelial cell monolayer

Cited by 13 publications

References 40 publications

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

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

Combination of Fluoride and SO2 Induce DNA Damage and Morphological Alterations in Male Rat Kidney

Dietary High Sodium Fluoride Impairs Digestion and Absorption Ability, Mucosal Immunity, and Alters Cecum Microbial Community of Laying Hens

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