Fluoride exposure regulates the elongation phase of protein synthesis in cultured Bergmann glia cells

Flores-Méndez, Marco; Palma‐Ramírez, D.; Alamillo, Nely; Hernández‐Kelly, Luisa C.; Razo, Luz M. Del; Ortega, Arturo

doi:10.1016/j.toxlet.2014.06.022

Cited by 24 publications

(12 citation statements)

References 32 publications

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“…The most important factor contributing to the exposure is the content of fluorine in drinking water and, to a lesser extent, in air and food [2, 3]. Moreover, this element is commonly used in the prevention of dental caries due to its effectiveness and the low costs of manufacture of products for oral care [2, 4–6]. …”

Section: Introductionmentioning

confidence: 99%

“…Of the received fluorine, 75 %–90 % undergoes absorption in the stomach and intestines, and 99 % of the fluorine that gets to the circulatory system is transported to tissues rich in calcium (mainly to hard tissues). Retrospective studies showed that the symptoms of fluorosis (the disorder of the physiology of bones and teeth and the damage to soft tissue) appeared when the supply of fluorine was over 0.15 mg/kg/24 h [2, 3, 6–9]. In recent years, scientists have been focusing on the toxic influence of this element on the nervous system.…”

Section: Introductionmentioning

confidence: 99%

“…One of the more important functions of BGC is the metabolism of glutamate. These cells are one of the main sources of this neurotransmitter, and to a large extent, they are responsible for glutamatergic stimulation [6, 72]. The incubation of BGC cells (isolated from the cerebellum of rats) with fluorine in concentrations of 1 and 2 mM caused a significant decrease in the lifespan of cells, causing disorders in the metabolism of glutamate [6, 73].…”

Section: Introductionmentioning

confidence: 99%

“…These cells are one of the main sources of this neurotransmitter, and to a large extent, they are responsible for glutamatergic stimulation [6, 72]. The incubation of BGC cells (isolated from the cerebellum of rats) with fluorine in concentrations of 1 and 2 mM caused a significant decrease in the lifespan of cells, causing disorders in the metabolism of glutamate [6, 73]. Other research showed a decrease in the concentration of glutamate in the serum, hippocampus and cerebral cortex of the studied animals (the concentration of fluorine in drinking water, 120 mg/L), an increase in the activity of glutamic acid decarboxylase and a decrease in the activity of asparagine transferase and alanine transferase—the enzymes participating in the metabolism of glutamate (the concentration of fluorine in drinking water, 150 mg/L) [66, 69, 74].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The Influence of Fluorine on the Disturbances of Homeostasis in the Central Nervous System

Dec

Łukomska

Maciejewska

et al. 2016

Biol Trace Elem Res

115

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Fluorides occur naturally in the environment, the daily exposure of human organism to fluorine mainly depends on the intake of this element with drinking water and it is connected with the geographical region. In some countries, we can observe the endemic fluorosis—the damage of hard and soft tissues caused by the excessive intake of fluorine. Recent studies showed that fluorine is toxic to the central nervous system (CNS). There are several known mechanisms which lead to structural brain damage caused by the excessive intake of fluorine. This element is able to cross the blood-brain barrier, and it accumulates in neurons affecting cytological changes, cell activity and ion transport (e.g. chlorine transport). Additionally, fluorine changes the concentration of non-enzymatic advanced glycation end products (AGEs), the metabolism of neurotransmitters (influencing mainly glutamatergic neurotransmission) and the energy metabolism of neurons by the impaired glucose transporter—GLUT1. It can also change activity and lead to dysfunction of important proteins which are part of the respiratory chain. Fluorine also affects oxidative stress, glial activation and inflammation in the CNS which leads to neurodegeneration. All of those changes lead to abnormal cell differentiation and the activation of apoptosis through the changes in the expression of neural cell adhesion molecules (NCAM), glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF) and MAP kinases. Excessive exposure to this element can cause harmful effects such as permanent damage of all brain structures, impaired learning ability, memory dysfunction and behavioural problems. This paper provides an overview of the fluoride neurotoxicity in juveniles and adults.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Influence of Fluorine on the Disturbances of Homeostasis in the Central Nervous System

Dec

Łukomska

Maciejewska

et al. 2016

Biol Trace Elem Res

115

View full text Add to dashboard Cite

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“…AD is characterized by an abnormal increase of variety of inflammatory cytokines and chemokines in the brain which is associated with an immunological response of activated microglial cells [20]. Fluoride treatment could lead to degeneration of glial cells, and glial cells were as targets of fluoride toxicity and involved in dysfunction of the brain induced by fluoride [21,22]. In addition, glial activation and inflammatory response were seen and a close link between oxidative stress neuroinflammation and degeneration in aluminum-fluoride toxicity rats was observed.…”

Section: Introductionmentioning

confidence: 99%

Fluoride-Induced Neuron Apoptosis and Expressions of Inflammatory Factors by Activating Microglia in Rat Brain

Yan

Liu

et al. 2015

Mol Neurobiol

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Excessive exposure to fluoride results in structural and functional damages to the central nervous system (CNS), and neurotoxicity of fluoride may be associated with neurodegenerative changes. Chronic microglial activation appears to cause neuronal damage through producing proinflammatory cytokines and is involved in many neurodegenerative disorders. It is not known about effects on microglia of fluoride. In the present study, healthy adult Wistar rats were exposed to 60 and 120 ppm fluoride in drinking water for 10 weeks, and control rats received deionized water. After 10 weeks, rats were sacrificed under anesthesia then apoptosis in neuron and inflammatory factors secreted by microglia were determined. We found that apoptosis of neurons in fluoride-treated rat brain increased and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive immunofluorescence increased with increasing fluoride concentrations. Bax protein expression increased and Bcl-2 protein expression decreased in fluoride-treated rat brain compared with that of the control rat brain. The microglia in the hippocampus and cortex of fluoride-treated rats were activated by immunostaining with OX-42, a marker of activated microglia, and OX-42-positive microglia cells were more abundant in the hippocampus than in the cortex. The levels of IL-1β and IL-6 protein expression in OX-42-labeled microglial cells were significantly increased in the cortex and hippocampus of rats exposed to fluoride, and TNF-α immunoreactivity in microglial cells of the hippocampus was significantly higher in the 120 ppm fluoride-treated group than that in the control group. Our results indicate that fluoride induced neuron apoptosis and expressions of inflammatory factors by activating microglia in rat brain.

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Toxicity of fluoride: critical evaluation of evidence for human developmental neurotoxicity in epidemiological studies, animal experiments and in vitro analyses

et al. 2020

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Recently, epidemiological studies have suggested that fluoride is a human developmental neurotoxicant that reduces measures of intelligence in children, placing it into the same category as toxic metals (lead, methylmercury, arsenic) and polychlorinated biphenyls. If true, this assessment would be highly relevant considering the widespread fluoridation of drinking water and the worldwide use of fluoride in oral hygiene products such as toothpaste. To gain a deeper understanding of these assertions, we reviewed the levels of human exposure, as well as results from animal experiments, particularly focusing on developmental toxicity, and the molecular mechanisms by which fluoride can cause adverse effects. Moreover, in vitro studies investigating fluoride in neuronal cells and precursor/stem cells were analyzed, and 23 epidemiological studies published since 2012 were considered. The results show that the margin of exposure (MoE) between no observed adverse effect levels (NOAELs) in animal studies and the current adequate intake (AI) of fluoride (50 µg/kg b.w./day) in humans ranges between 50 and 210, depending on the specific animal experiment used as reference. Even for unusually high fluoride exposure levels, an MoE of at least ten was obtained. Furthermore, concentrations of fluoride in human plasma are much lower than fluoride concentrations, causing effects in cell cultures. In contrast, 21 of 23 recent epidemiological studies report an association between high fluoride exposure and reduced intelligence. The discrepancy between experimental and epidemiological evidence may be reconciled with deficiencies inherent in most of these epidemiological studies on a putative association between fluoride and intelligence, especially with respect to adequate consideration of potential confounding factors, e.g., socioeconomic status, residence, breast feeding, low birth weight, maternal intelligence, and exposure to other neurotoxic chemicals. In conclusion, based on the totality of currently available scientific evidence, the present review does not support the presumption that fluoride should be assessed as a human developmental neurotoxicant at the current exposure levels in Europe.

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Fluoride exposure regulates the elongation phase of protein synthesis in cultured Bergmann glia cells

Cited by 24 publications

References 32 publications

The Influence of Fluorine on the Disturbances of Homeostasis in the Central Nervous System

The Influence of Fluorine on the Disturbances of Homeostasis in the Central Nervous System

Fluoride-Induced Neuron Apoptosis and Expressions of Inflammatory Factors by Activating Microglia in Rat Brain

Toxicity of fluoride: critical evaluation of evidence for human developmental neurotoxicity in epidemiological studies, animal experiments and in vitro analyses

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