Effects of dietary protein and calcium on thymus apoptosis induced by fluoride in female rats (Wistar rats)

Wang, Hongwei; Zhou, Baosen; Cao, Jianhua; Gu, Xinli; Cao, Chunfang; Wang, Jundong

doi:10.1002/tox.20421

Cited by 36 publications

(26 citation statements)

References 34 publications

(28 reference statements)

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“…Nevertheless, an excessive fluoride ingestion by Wistar rats induced a significant upregulation of caspase-3 and caspase-9 mRNA expression levels in thymus cells and induced thymus apoptosis [37]. Considerable enhancement of both caspase-9 and caspase-3 activities, indicating that fluoride induced caspase-dependent apoptosis, was also observed in the hepatocytes of fluoride-intoxicated pigs [30].…”

Section: Caspasesmentioning

confidence: 93%

“…Many of these cellular events ultimately lead to cell death. NaFinduced apoptosis was demonstrated in the cells from different organs and tissues including lungs [25,26], kidneys [27,28], liver [29][30][31], brain [32][33][34], pancreas [35,36], thymus [37], endometrium [38,39], bone marrow [40], hair follicles [41], erythrocytes [42][43][44], as well as leukemic cells [45][46][47].…”

Section: Fluoride-induced Toxicity and Cell Deathmentioning

confidence: 99%

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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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Section: Caspasesmentioning

confidence: 93%

Section: Fluoride-induced Toxicity and Cell Deathmentioning

confidence: 99%

Molecular Mechanisms of Cytotoxicity and Apoptosis Induced by Inorganic Fluoride

2012

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“…It has been demonstrated that a high intake of fluoride results in Electronic supplementary material The online version of this article (doi:10.1007/s12011-015-0458-5) contains supplementary material, which is available to authorized users. damage to T cells in the thymus of animals [3,11]. However, very little attention has focused on the underlying molecular mechanisms.…”

Section: Introductionmentioning

confidence: 99%

“…It is well known that fluoride is an essential mineral element required by mammals and humans for bone health and that it is used as an effective prophylactic for dental caries at low doses [2]. However, fluoride is also known to be cytotoxic to many types of cells at high concentrations [3][4][5]. Millions of people worldwide are reported to be affected by fluoride toxicity from drinking water containing high concentrations of fluoride, particularly in China [6,7].…”

Section: Introductionmentioning

confidence: 99%

Modulation and the Underlying Mechanism of T Cells in Thymus of Mice by Oral Administration of Sodium Fluoride

Yin

Song

et al. 2015

Biol Trace Elem Res

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The underlying mechanism of thymic T cell regulation has been a hot topic of research in recent years. Fluoride is toxic at high concentrations and fluoride toxicity to thymic T cells was assessed in our study. To explore T cell responses to excess fluoride, different concentrations of fluoride were uptake by mice for 6 weeks. The expression of genes, including Foxn1, Cbx4, DLL4, and IL-7 gene, associated with the development and differentiation of T cells in thymic epithelial cells(TECs) was lower in the experimental groups than that in the control group. The percentages of CD4(+) and CD8(+) T cells that decreased with the fluoride administration were confirmed by flow cytometry. The mRNA levels of immunoregulatory cytokines IL-2 and IL-10, which participate in T cell proliferation, also declined in the experimental groups as compared with the control group. Expression of the T cell function-related genes CD2, PTPRC, CD69, and CD101, which are involved in thymic function in mice, decreased with the fluoride administration. Our findings suggest that the administration of high concentrations of fluoride to mice induces a decrease in CD4(+) and CD8(+) thymus T cells by harming TECs leading to the dysfunction of the thymus by altering the expression of T cell function-related genes and immunoregulatory cytokine production.

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“…Then furthermore epidemiological researches and experimental studies show that it also affects the nervous system [1,2], reproductive system [3,4], cardiovascular system [5,6], immune system [7][8][9], and so on. Our previous studies showed that excessive fluoride ingestion induced pathological changes in the spleen and impairment of immune function in rabbits [10,11] and thymus apoptosis in female rats [12]. Extravasation of circulating lymphocytes into lymphoid and extra-lymphoid tissue is essential in normal immune surveillance and inflammation [13].…”

Section: Introductionmentioning

confidence: 99%

Effect of Fluoride on Endocytosis and Surface Marker Expression Levels of Mouse B Cells In Vitro

Shi

Dong

et al. 2016

Cell Physiol Biochem

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Background/Aims: To clarify the effect of fluoride on splenic B cells, the endocytosis and surface marker expression levels of mouse splenic B cells were detected in vitro by flow cytometry. Methods: Cells were stimulated with 10 µg/mL lipopolysaccharide (LPS) and varying concentrations of Sodium Fluoride (NaF) (0, 50 µM, 100 µM, 500 µM, 1000 µM). Results: The results demonstrated that the endocytic capacity of B cells was enhanced by NaF at 50µM. NaF significantly enhanced CD80 expression at 50 µM and decreased CD86 expression at 500 µM. CD40 and CD138 expression on B cells were down-regulated at varying high concentrations of NaF. Conclusion: our results showed that the endocytic capacity, expression levels of CD40 and CD80 of B cells changed significantly at lower concentrations, whereas expression levels of CD138 and CD86 changed significantly at higher concentrations, suggesting that fluoride could inhibit immune function in animals.

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Effects of dietary protein and calcium on thymus apoptosis induced by fluoride in female rats (Wistar rats)

Cited by 36 publications

References 34 publications

Molecular Mechanisms of Cytotoxicity and Apoptosis Induced by Inorganic Fluoride

Molecular Mechanisms of Cytotoxicity and Apoptosis Induced by Inorganic Fluoride

Modulation and the Underlying Mechanism of T Cells in Thymus of Mice by Oral Administration of Sodium Fluoride

Effect of Fluoride on Endocytosis and Surface Marker Expression Levels of Mouse B Cells In Vitro

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