Effects of fluoride on the expression of NCAM, oxidative stress, and apoptosis in primary cultured hippocampal neurons

Zhang, Ming; Wang, Aiguo; He, Weidong; He, Ping; Xu, Bo; Xia, Tao; Chen, Xuemin; Yang, Kun

doi:10.1016/j.tox.2007.04.007

Cited by 150 publications

(106 citation statements)

References 38 publications

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“…Fluoride is eliminated (50-80%) by kidney, therefore kidneys are also very sensitive to fluoride toxication [8]. It has been reported that some biochemical parameters change due to increased oxidative stress in fluoride toxication [10]. In our study, the total protein and albumin levels decreased in fluoride exposed rabbits compared to the control rabbits.…”

Section: Discussionsupporting

confidence: 42%

“…Enzyme ALT revealed a statistically significant increase (p<0.05), while enzyme AST increased slightly but the latter was not statistically significant. Likewise, a statistically significant increase in ALT and AST enzymes have been reported in mice, suckling pups [31], and rat subjects [10,40]. Kidney is one of the target organs for development of fluorosis toxication [41].…”

Section: Naf Groupmentioning

confidence: 99%

“…Pathological changes occur in liver, kidney, heart, muscle, gastro-intestinal tract, and skeletal system, as a result of fluorosis [9]. In fluoride toxication, changes have been reported in biochemical parameters, due to elevation of oxidative stress [10]. Fluoride toxication results from increasing fluoride ions, which lead to inhibition of glycoprotein synthesis [11].…”

Section: Introductionmentioning

confidence: 99%

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Effect of Fluoride Exposure on Serum Glycoprotein Pattern and Sialic Acid Level in Rabbits

Çiftçi

Çenesiz

Yarım

et al. 2009

Biol Trace Elem Res

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This study describes the effects of fluoride exposure on the protein profile, glycoprotein pattern, and total sialic acid concentration of serum in rabbits. For this aim; 20 healthy New Zealand rabbits were used. The rabbits were divided into two equal groups each with ten animals according to their weighing: control group and experimental group. The rabbits in control group were given drinking tap water containing 0.29 mg/l sodium fluoride and experimental group received the same tap water to which was added 40 mg/l sodium fluoride for 70 days. Blood samples were taken from each rabbit on day 70. Serum fluoride concentrations were measured by a fluoride-specific ion electrode in serum. The fluoride levels in the serum were found as 18.4 (±1.58) μg/L in control and 301.3 (±52.18) μg/L in fluoride exposed rabbits. The sialic acid levels were found as 69.2 (±0.32) mg/dL in control and 43.4 (±0.13) mg/dL in fluoride exposed group. The electrophoretic patterns of serum proteins, glycoproteins, and total sialic acid concentration were determined. Fifteen different protein fractions with molecular weights ranging from 22 to 249 kDa were displayed in the serum protein electrophoretic gel of both groups. The raw concentrations of the protein fractions decreased in fluoride exposed rabbits as compared with the control rabbits. The serum glycoprotein pattern revealed seven major protein bands from 47 to 167 kDa in experimental and control groups. The slight decrease of raw concentration of the protein bands in glycoprotein pattern of serum was observed in fluoride toxication comparing to control. The

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Section: Discussionsupporting

confidence: 42%

Section: Naf Groupmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of Fluoride Exposure on Serum Glycoprotein Pattern and Sialic Acid Level in Rabbits

Çiftçi

Çenesiz

Yarım

et al. 2009

Biol Trace Elem Res

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“…Alterations in these proteins activities can trigger apoptotic cascade involving p53, what leads to chromosomal instability and activation of the p53-dependent mitotic checkpoint, that is, disturbance of normal cell cycle and induction of apoptosis. Zhang et al [33,148], studying the mechanisms underlying the neurotoxicity of fluorosis on the primary rat hippocampal neurons, reported that high fluoride intake, in addition to DNA damage and cell-cycle regulation, suppressed the expression of neural cell adhesion molecules (NCAMs), necessary for the maintenance of cognitive functions of brain such as learning and memory, but enhanced the gene expression of NF-κB, the transcription factors which can both promote cell death in response to oxidative stress, thus contributing to neurological dysfunctions.…”

Section: Gene Expressionmentioning

confidence: 99%

Molecular Mechanisms of Cytotoxicity and Apoptosis Induced by Inorganic Fluoride

2012

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Fluoride (F) is ubiquitous natural substance and widespread industrial pollutant. Although low fluoride concentrations are beneficial for normal tooth and bone development, acute or chronic exposure to high fluoride doses results in adverse health effects. The molecular mechanisms underlying fluoride toxicity are different by nature. Fluoride is able to stimulate G-proteins with subsequent activation of downstream signal transduction pathways such as PKA-, PKC-, PI3-kinase-, Ca 2+ -, and MAPK-dependent systems. G-protein-independent routes include tyrosine phosphorylation and protein phosphatase inhibition. Along with other toxic effects, fluoride was shown to induce oxidative stress leading to excessive generation of ROS, lipid peroxidation, decrease in the GSH/GSSH ratio, and alterations in activities of antioxidant enzymes, as well as to inhibit glycolysis thus causing the depletion of cellular ATP and disturbances in cellular metabolism. Fluoride triggers the disruption of mitochondria outer membrane and release of cytochrome c into cytosol, what activates caspases-9 and -3 (intrinsic) apoptotic pathway. Extrinsic (death receptor) Fas/FasL-caspase-8 and -3 pathway was also described to be implicated in fluoride-induced apoptosis. Fluoride decreases the ratio of antiapoptotic/proapoptotic Bcl-2 family proteins and upregulates the expression of p53 protein. Finally, fluoride changes the expression profile of apoptosis-related genes and causes endoplasmic reticulum stress leading to inhibition of protein synthesis.

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“…Although the effect of NaF on spermatozoa and male fertility has been well-researched over the last few decades (Pushpalatha et al, 2005;Zhang et al, 2007; Dvora 0 kova 0 -Hortova 0 et al Spittle, 2009;Sun et al, 2010), several fundamental queries remain unanswered. For example, what are the molecular mechanisms by which NaF regulates different key processes in spermatozoa, including motility, capacitation, and the acrosome reaction?…”

Section: Introductionmentioning

confidence: 99%

Effect of sodium fluoride on male mouse fertility

et al. 2015

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SUMMARYSodium fluoride (NaF), an environmental pollutant, has been tested for its impact on fertility in several species of laboratory animals. A literature demonstrated that NaF adversely affects sperm motility, morphology, capacitation, and the acrosome reaction. However, the molecular mechanisms underlying these alterations have not yet been elucidated. Therefore, present study was designed to evaluate the regulatory pathways involved in the effect of NaF on sperm function and fertilization. In this in vitro study, mouse spermatozoa were incubated with a range of concentrations (2.5, 5, and 10 mM) of NaF for 90 min in media that support in vitro fertilization. Our results showed that NaF was associated with reduced intracellular ATP generation, motility, and motion kinematics. Likewise, short-term exposure of spermatozoa to NaF significantly reduced the intracellular calcium concentration, protein kinase-A activity, and tyrosine phosphorylation of sperm proteins, which were associated with a significant decrease in the rate of capacitation and the acrosome reaction. Finally, NaF significantly reduced the fertilization and blastocyst formation during early embryonic development. On the basis of these results, we propose that NaF reduces sperm motility, capacitation, and the acrosome reaction leading to poor fertilization and suppressed embryonic development.

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Effects of fluoride on the expression of NCAM, oxidative stress, and apoptosis in primary cultured hippocampal neurons

Cited by 150 publications

References 38 publications

Effect of Fluoride Exposure on Serum Glycoprotein Pattern and Sialic Acid Level in Rabbits

Effect of Fluoride Exposure on Serum Glycoprotein Pattern and Sialic Acid Level in Rabbits

Molecular Mechanisms of Cytotoxicity and Apoptosis Induced by Inorganic Fluoride

Effect of sodium fluoride on male mouse fertility

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