Changes in energy metabolism induced by fluoride: Insights from inside the mitochondria

Araújo, Tamara Teodoro; Pereira, Hugo Juarez Vieira; Dionízio, Aline; Sanchez, Camila do Carmo; Carvalho, Thamyris de Souza; Fernandes, Marcelo; Buzalaf, Marília Afonso Rabelo

doi:10.1016/j.chemosphere.2019.124357

Cited by 37 publications

(47 citation statements)

References 68 publications

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“…In our analyses, we observed an increase in LPO and NO in the group exposed to 50 mg F/L and the reduction of antioxidant capacity in both exposure groups, which reveals the occurrence of an imbalance in the cellular redox system, suggesting the presence of oxidative stress. These finding corroborate with the data in the literature about the fluoride ability to promote ROS generation and changes in cellular antioxidant defenses [ 2 , 37 , 38 ].…”

Section: Discussionsupporting

confidence: 92%

“…These mitochondrial changes lead to a higher generation of ROS that induces the action of cellular antioxidant compounds, however if this level of ROS is too high, cells tend not to be able to intercept these compounds resulting in oxidative damage [ 43 ]. Furthermore, the antioxidant system is also the target of the toxic action of fluoride as evidenced in some previous studies [ 37 , 38 , 44 , 45 , 46 ].…”

Section: Discussionmentioning

confidence: 95%

“…Among the cellular toxicity mechanisms of fluoride there is oxidative stress [ 37 , 38 ]. This event is featured by an increase in reactive oxygen species (ROS) to the detriment of antioxidant cell response.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 95%

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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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“…However, in this study, the protein extraction and proteomic analysis protocols followed a recently developed methodology that increases the identification of proteins in in vivo acquired enamel pellicle samples [22]. We highlight that the analysis of pooled samples has been widely used in proteomic studies involving quantitative analysis of acquired pellicle [20,22,[25][26][27][28][29][30]. Moreover, in this study, the proteins were individually extracted, and a biological triplicate was done.…”

Section: Discussionmentioning

confidence: 99%

Proteomic profile of the acquired enamel pellicle of professional wine tasters with erosive tooth wear

Silva

Ventura

Oliveira

et al. 2021

European J Oral Sciences

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The aim of this study was to compare the acquired enamel pellicle protein profile of professional wine tasters with mild and moderate erosive tooth wear. Twelve professional wine tasters participated (3 from a low tooth wear group; 9 from a high tooth wear group). Acquired enamel pellicle samples were collected and processed for proteomic analysis (nLC-ESI-MS/MS). The acquired enamel pellicle proteomic profile was different between the groups. The proteins found exclusively in the low

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“…Because the metabolic evaluation has suggested an increased redox potential of U87 glial cells under F toxicity and several studies have hypothesized that neurological damages after F consumption may be related to oxidative stress [52][53][54] we, then, sought to assess whether the toxic effects observed in U87 glial cells would be due to oxidative-induced misbalance. Oxidative stress biomarkers after 10 days of exposure were performed by measuring H 2 O 2 levels, since it is well recognized that H 2 O 2 is the final product of other ROS and has the longest halflife.…”

Section: Plos Onementioning

confidence: 99%

Human cultured IMR-32 neuronal-like and U87 glial-like cells have different patterns of toxicity under fluoride exposure

et al. 2021

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Background Fluoride (F) is a naturally exists in nature but several studies have indicated it as an environmental toxicant to all leaving beings. Human F exposure has increased over the years since this ion has been used by industry on foods, beverages, toothpastes and on water supply. Although F is safe at optimal concentrations in water supply, human exposure to high levels could trigger neurofunctional deficits. Materials and methods In this study, human glial-like (U87) and neuronal-like (IMR-32) cells lineages were used to access F toxicity and CNS cell sensibility on both cell facing the same protocol. Cells were exposed to F over 3, 5 and 10 days on two different F concentrations. Fluoride exposed cells were evaluated by standard toxicity assays to cell viability, apoptosis, necrosis and general cell metabolism. Oxidative stress parameters were evaluated by ATP and ROS levels, lipid peroxidation, GSH/GSSG ratio and comet assay. Results No changes were observed in IMR-32 at any given time while after 10 days of exposure to 0.22μg/mL, U87 glial-like cells showed signs of toxicity such as decreased cell viability by necrosis while general cell metabolism was increased. Oxidative stress parameters were next evaluated only on U87 glial-like cells after 10 days of exposure. F induced a decrease on ATP levels while no changes were observed on reactive oxygen species and lipid peroxidation. GSH/GSSG ratio was decreased followed by DNA damage both on 0.22μg/mL F. Conclusions Our results suggest an important differential behavior of the distinct types of cells exposed to the different fluoride concentrations, pointing that the U87 glial-like cells as more susceptible to damage triggered by this ion.

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Changes in energy metabolism induced by fluoride: Insights from inside the mitochondria

Cited by 37 publications

References 68 publications

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

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

Proteomic profile of the acquired enamel pellicle of professional wine tasters with erosive tooth wear

Human cultured IMR-32 neuronal-like and U87 glial-like cells have different patterns of toxicity under fluoride exposure

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