Sodium Fluoride Treatment Research Articles

Does Dactyloctenium aegyptium ethanolic extract protect against hormonal, histological and immunohistochemical alterations induced by sodium fluoride in rat adrenal gland?

ABSTRACT This work aimed to perform a biochemical, histological, and immunohistochemical assessment of the influence of sodium fluoride on the adrenal gland of rats and the possible ameliorating role of Dactyloctenium aegyptium (D. aegyptium). Thirty-five male albino rats were divided into five equal groups: group I served as the control group, group II received sodium fluoride (5 mg/kg), group III received D. aegyptium (200 mg/kg), and groups IV and V received sodium fluoride and D. aegyptium (100 and 200 mg/kg respectively) simultaneously for 28 days. Aldosterone, corticosterone, nitric oxide, sodium, potassium, and chloride were measured in serum samples. Adrenal gland specimens were processed for histological, histochemical, and immunohistochemical studies. The sodium fluoride group recorded a significant reduction in serum levels of aldosterone, corticosterone, potassium, and chloride (p ≤ 0.0001) and a significant increase in nitric oxide (p ≤ 0.0001) and serum sodium (p = 0.0076) when compared with the control group. Histological changes in the sodium fluoride treated group showed cytoplasmic vacuolation, scattered apoptotic cells, and hemorrhage. The sodium fluoride treatment significantly decreased glycogen (p = 0.0002), total protein) p = 0.0007), and DNA (p ≤ 0.0001) and increased inducible nitric oxide synthase (p = 0.0001). Co-treated groups with D. aegyptium showed almost average values for most parameters and a nearly standard architecture. The present data answers the question of our research that D. aegyptium ethanolic extract could protect against sodium fluoride’s adverse effects in rat adrenal glands on the physiological and histological levels.

Increased <i>Arabidopsis thaliana</i> cell culture resistance to sodium fluoride by constitutive expression of HSP101

Fluorine is one of the toxic elemental components of industrial emissions. Increased fluoride content in the atmosphere, soil or water negatively affects the growth and development of plants, as well as reducing resistance to various environmental stressors. An increase in ambient temperature causes a protective response in all organisms taking the form heat shock protein synthesis. The specific protein HSP101, which performs the function of protecting plant cells from heat damage, is also responsible for inducible thermotolerance, representing the ability of organisms to withstand the effects of severe heat shock that were previously exposed to mild heat stress, as a result of which heat shock proteins are induced. Heat shock proteins are involved in protecting not only against elevated temperatures, but also various other stress factors. In this work, the effect of sodium fluoride treatment on the viability of Arabidopsis thaliana cell culture, expression and synthesis of heat shock proteins was studied along with the role of heat shock protein HSP101 in providing resistance to fluoride. Sodium fluoride has been shown to significantly reduce the viability of A. thaliana cells by suppressing the activation of HSP101 gene expression with an increase in temperature. At the same time, the A. thaliana line, which has constitutive expression of the HSP101 gene, proved to be more resistant to the toxic effects of sodium fluoride.

Fluoride disrupts intestinal epithelial tight junction integrity through intracellular calcium-mediated RhoA/ROCK signaling and myosin light chain kinase

Fluoride is a common contaminant of groundwater and agricultural commodity, which poses challenges to animal and human health. A wealth of research has demonstrated its detrimental effects on intestinal mucosal integrity; however, the underlying mechanisms remain obscure. This study aimed to investigate the role of the cytoskeleton in fluoride-induced barrier dysfunction. After sodium fluoride (NaF) treatment of the cultured Caco-2 cells, both cytotoxicity and cytomorphological changes (internal vacuoles or massive ablation) were observed. NaF lowered transepithelial electrical resistance (TEER) and enhanced paracellular permeation of fluorescein isothiocyanate dextran 4 (FD-4), indicating Caco-2 monolayers hyperpermeability. In the meantime, NaF treatment altered both the expression and distribution of the tight junction protein ZO-1. Fluoride exposure increased myosin light chain II (MLC2) phosphorylation and triggered actin filament (F-actin) remodeling. While inhibition of myosin II by Blebbistatin blocked NaF-induced barrier failure and ZO-1 discontinuity, the corresponding agonist Ionomycin had effects comparable to those of fluoride, suggesting that MLC2 serves as an effector. Given the mechanisms upstream of p-MLC2 regulation, further studies demonstrated that NaF activated RhoA/ROCK signaling pathway and myosin light chain kinase (MLCK), strikingly increasing the expression of both. Pharmacological inhibitors (Rhosin, Y-27632 and ML-7) reversed NaF-induced barrier breakdown and stress fiber formation. The role of intracellular calcium ions ([Ca2+]i) in NaF effects on Rho/ROCK pathway and MLCK was investigated. We found that NaF elevated [Ca2+]i, whereas chelator BAPTA-AM attenuated increased RhoA and MLCK expression as well as ZO-1 rupture, thus, restoring barrier function. Collectively, abovementioned results suggest that NaF induces barrier impairment via Ca2+-dependent RhoA/ROCK pathway and MLCK, which in turn triggers MLC2 phosphorylation and rearrangement of ZO-1 and F-actin. These results provide potential therapeutic targets for fluoride-induced intestinal injury.

In vitroSodium Fluoride Treatment Significantly Affects Apoptosis and Proliferation in the Liver of Embryonic Chickens

Sodium fluoride (NaF), although helpful in preventing dental decay, may negatively affect the body. The aim of this study was to examine the effects of a 6-hin vitrotreatment of livers isolated from 14-day-old chicken embryos with NaF at doses of 1.7 (D1), 3.5 (D2), 7.1 (D3) and 14.2 mM (D4), with regard to apoptosis, cell proliferation and tissue structure. The mRNA expression of the apoptosis regulatorsCYCS,APAF1,BCL2,CASP3,CASP9andTMBIM1was analysed by the qPCR method. Apoptotic cells were detected by a TUNEL assay. The tissue and DNA structure were also analysed by histological staining (H&E, Feulgen). The number of proliferating cells was determined and the apoptosis regulatory proteins were localised by the immunohistochemical staining of PCNA, CASP3 and APAF1. The results showed that the mRNA expression ofCYCS,BCL2,CASP3,CASP9andAPAF1increased significantly in the D1 group, as did that ofCASP9in the D3 group and ofBCL2andAPAF1in the D4 group. The number of apoptotic cells increased significantly in the D4 group, where they increased from 18% to 49%. On the other hand, the number of proliferating cells decreased gradually, in a dose-dependent manner, from 84% in the control group to 5.5% in the D4 group. The expression of apoptosis-regulating factors also increased: in the D3 and D4 groups, the CASP3 immunopositive reaction was more intensive in single cells in the embryonic livers, whereas that of APAF1 increased in the hepatocytes as well as in the hepatic blood vessel walls. The mechanism of the effect of NaF on apoptosis in the embryonic liver is very complex. In the groups exposed to higher doses of NaF, apoptosis was significantly stimulated, while proliferation was inhibited and the tissue structure was damaged. The expression of apoptosis regulators at the mRNA and protein levels increased, but the mRNA expression did not depend on the NaF dose. These results reveal that NaF, by changing the balance between apoptosis and the proliferation of hepatocytes, may disturb the development and function of the liver in embryonic chickens. Therefore, the risk of exposure to NaF should be considered when determining the standards for human and animal exposure to this compound.

Fluoroacetate distribution, response to fluoridation, and synthesis in juvenile Gastrolobium bilobum plants

Like angiosperms from several other families, the leguminous shrub Gastrolobium bilobum R.Br. produces and accumulates fluoroacetate, indicating that it performs the difficult chemistry needed to make a C–F bond. Bioinformatic analyses indicate that plants lack homologs of the only enzymes known to make a C–F bond, i.e., the Actinomycete flurorinases that form 5′-fluoro-5′-deoxyadenosine from S-adenosylmethionine and fluoride ion. To probe the origin of fluoroacetate in G. bilobum we first showed that fluoroacetate accumulates to millimolar levels in young leaves but not older leaves, stems or roots, that leaf fluoroacetate levels vary >20-fold between individual plants and are not markedly raised by sodium fluoride treatment. Young leaves were fed adenosine-13C-ribose, 13C-serine, or 13C-acetate to test plausible biosynthetic routes to fluoroacetate from S-adenosylmethionine, a C3-pyridoxal phosphate complex, or acetyl-CoA, respectively. Incorporation of 13C into expected metabolites confirmed that all three precursors were taken up and metabolized. Consistent with the bioinformatic evidence against an Actinomycete-type pathway, no adenosine-13C-ribose was converted to 13C-fluoroacetate; nor was the characteristic 4-fluorothreonine product of the Actinomycete pathway detected. Similarly, no 13C from acetate or serine was incorporated into fluoroacetate. While not fully excluding the hypothetical pathways that were tested, these negative labeling data imply that G. bilobum creates the C–F bond by an unprecedented biochemical reaction. Enzyme(s) that mediate such a reaction could be of great value in pharmaceutical and agrochemical manufacturing.

Effect of <i>Ginkgo biloba</i> extract on Histomorphometric changes of Hippocampus against Fluoride Toxicity in Wistar Rats

Prolonged ingestion of fluoride leads to the pathogenesis known as fluorosis. Fluoride exposure leads to neuro degenerative changes such as reduction in the neuronal cell size and number. Exposure to fluoride showed neurodegenerative changes like shrunken neurons, increased in folding of the nuclear membrane, mitochondrial alterations, and dilated rough endoplasmic reticulum cisternae and clusters of vesicles near the Golgi bodies. Present study is to explore the histomorphometric changes of the hippocampus of fluoride induced brain and treated with Ginkgo biloba Extract (GBE). Thirty number (30) adult male Wistar rats were randomly separated into 5 Groups (n=6). Group1 (Control) supplemented with water, 2 to 5 Groups were supplemented with 100ppm of sodium fluoride for 30 days, while the Groups 3, 4, and 5 were Ginkgo biloba extract treated at 50mg/ kg, 100mg/kg and 200mg/kg body weight for 15 days, after sodium fluoride treatment, results showed that, 200mg/kg GBE provided effective and complete protection against fluoride toxicity. From the present study concluded that 50, 100 and 200 mg/kg GBE was significantly attenuated the fluoride induced toxicity in a dose depending manner. Present histomorphometrical study showed delayed neuronal death in the CA1 and CA3 regions of hippocampus of fluoride group that was significantly attenuated by GBE (50,100 and 200 mg/kg) in a dose dependant manner.

The Effects of Sodium Fluoride (NaF) Treatment on the PI3K/Akt Signal Pathway in NRK-52E Cells.

The effects of the element fluorine on the phosphoinositide-3-kinase-protein kinase B/Akt (PI3K/Akt) pathway has a significant role in regulation of intracellular molecular mechanisms. NRK-52E rat kidney epithelial cell line was selected as the material of the study. NaF was used as the fluorine source in the study. The NaF dose was determined with the MTT assay. The NaF concentrations were determined as the proliferation concentration of 10μM and IC25 (2250μM) and IC50 (4250μM) for 24h. In the study, the erb-b2 receptor tyrosine kinase 2 (ERBB2), phosphoinositide-3-kinase (PI3K), Protein kinase B (PKB,Akt), Mammalian target of rapamycin (mTOR), and the Tumor protein 53 (TP53) genes were considered as the target genes. NaF concentration was administered on the cells. Total mRNA was isolated. mRNAs were turned into cDNA. The expression levels of the target genes were determined by RT-qPCR method. According to the results obtained in the study, the low NaF concentration increased the expression levels of the ERBB2, PI3K, and Akt genes, while the higher concentrations did not significantly affect these levels. The expression of mTOR decreased at all given concentrations. The expression of the TP53 gene did not change at the low concentration, while it increased at the high concentrations. Based on the results, it may be stated that fluorine may inhibit the kinase enzymes in the PI3K/Akt pathway. In summary, in the pathogenesis of the cell damage caused by fluorine in the NRK-52E cell line, the PI3K/Akt/mTOR pathway is an important signal pathway.

Sodium Fluoride In Vitro Treatment Affects the Expression of Gonadotropin and Steroid Hormone Receptors in Chicken Embryonic Gonads.

Simple SummaryEffects of in vitro sodium fluoride (NaF) treatment on the mRNA expression of luteinizing hormone receptor (LHR), follicle-stimulating hormone receptor (FSHR), estrogen receptors (ESR1 and ESR2), progesterone receptor (PGR), and the immunolocalization of PGRs were examined in gonads of 14-day-old chicken embryos. In the ovary, the NaF treatment significantly increased mRNA levels of all investigated receptors. In the testes, the lowest applied dose of NaF (1.7 mM) significantly decreased the expression of FSHR, ESR1, ESR2, and PGR. Alternatively, the higher NaF dose (7.1 mM) elevated PGR mRNA level in the male gonad. Immunohistochemical analysis revealed that the NaF exposure increased PGR expression in the ovarian cortex, while it decreased its expression in the testes. Collectively, these data indicate that: (i) NaF may disturb the chicken embryonic development, and (ii) different mechanisms of this toxicant action exist within the female and male gonads.Sodium fluoride (NaF), in addition to preventing dental decay may negatively affect the body. The aim of this study was to examine the effect of a 6 h in vitro treatment of gonads isolated from 14-day-old chicken embryos with NaF at doses of 1.7 (D1), 3.5 (D2), 7.1 (D3), and 14.2 mM (D4). The mRNA expression of luteinizing hormone receptor (LHR), follicle-stimulating hormone receptor (FSHR), estrogen receptors (ESR1 and ESR2), progesterone receptor (PGR), and the immunolocalization of progesterone receptors were examined in the tissue. In the ovary, the expression of FSHR and LHR increased following the NaF treatment. In the case of FSHR the highest stimulatory effect was noticed in the D2 group, while the expression of LHR increased in a dose-dependent manner. A gradual increase in ESR1 and PGR mRNA levels was also observed in the ovary following the NaF treatment, but only up to the D3 dose of NaF. The highest ESR2 level was also found in the D3 group. In the testes, the lowest dose of NaF significantly decreased the expression of FSHR, ESR1, ESR2, and PGR. On the other hand, an increase in PGR expression was observed in the D3 group. The expression of LHR in the testes was not affected by the NaF treatment. Immunohistochemical analysis showed that NaF exposure increased progesterone receptor expression in the ovarian cortex, while it decreased its expression in the testes. These results reveal that NaF may disturb the chicken embryonic development and different mechanisms of this toxicant action exist within the females and males.

Ginkgo biloba ameliorates fluoride toxicity in rats by altering histopathology, serum enzymes of heme metabolism and oxidative stress without affecting brain mGluR5 gene

Background: To evaluate the therapeutic potential of Ginkgo biloba extract (GBE) in experimental model of fluorosis. Objectives: To study the protective effect of GBE in fluoride toxicity by assessment of oxidative stress, serum biochemical parameters, acetylcholinesterase (AChE) activity, histopathology and brain mGluR5 gene expression. Materials and Methods: Fifteen adult male Wistar rats were randomly assigned to 5 groups (n = 3 rats in each group). Group 1 (control) received water, Groups 2–5 were treated with 100 ppm of sodium fluoride for 30 days, while the Groups 3, 4 and 5 were GBE treated with 50 mg/kg, 100 mg/kg and 200 mg/kg body weight for 15 days, after sodium fluoride treatment for 30 days. Results: Elevated serum delta aminolevulinic acid dehydratase and delta aminolevulinic acid synthatase levels in fluoride intoxicated rats were ameliorated by various doses of GBE treatment. Elevated serum glutathione and decreased oxidized gluatathione levels observed in fluoride intoxicated rats were also ameliorated by GBE treatment but effectively at 100 mg/kg dose. Reduced AChE activity of hippocampus in fluoride-induced toxicity was reverted by 50 mg/kg of GBE whereas other doses (100 and 200 mg/kg) caused significant inhibition of AChE activity in comparison with fluoride group. Fluoride group rats showed significant reduction of mGluR5 gene expression levels whereas in all GBE treatment groups those changes Were not significantly reverted. GBE treatment to fluoride intoxicated rats almost reverted the degenerative changes in liver and kidney caused by fluorosis. Conclusion: The present study concluded beneficial effects of GBE in experimental model of fluorosis.

Assessment of Protective Role of Quinoa against Sodium Fluoride Induced Skeletal Deformities in Mice Fetuses

Rajasthan has the highest number of habitations where groundwater contains fluoride specifically in the region of Thar Desert. Infact, Pan India is affected by fluoride problem, but Rajasthan is the only state where almost all the districts are affected by high fluoride. High Fluoride concentration in drinking water has been shown to cause skeletal and dental abnormalities, besides others such as osteosclerosis. It has been shown through medical research that almost all the vital systems and organs in the body including thyroid, kidney, cardiovascular, gastrointestinal, endocrine, neurological, reproductive, developmental, molecular level, immunity etc. gets affected by concentration of Fluoride when it exceeds WHO standard values. This finding facilitated us to go in further and find the effect of Sodium Fluoride (NaF) when given to pregnant mice through drinking water at various fetal developmental stages with focus on study of developmental pattern of the skeletal system of growing fetuses followed by a protective role of phytomaterials against it. In this study Quinoa seed, were selected because of its high nutritive value and latest findings indicating its antiteratogenic nature. The study was planned in such a way that females in question were subjected to fluoride treatment prior to mating, during pregnancy and post partum period when weaning process is on. The observations clearly indicates that post Sodium fluoride treatment there was a reduction in size and general body weight of fetuses. Besides this, there was an increase in the number of immature fetuses. Various skeletal anomalies were also observed, such as partially ossified ribs, reduced skull ossification, reduced sternebrae etc. Chenopodium Quinoa, also called Superfood due to its high quality of protein and wide range of minerals and vitamins was used for its protective role as mentioned earlier. In this study NaF along with Quinoa seeds were administered to treated animals. These animals showed improvement in maternal weight, increase in body weight and size of fetuses as well as bone ossification. These findings suggest that Quinoa seeds possibly have a protective effect against Sodium Fluoride induced teratogenicity.

The leaf extracts of Camellia sinensis (green tea) ameliorate sodium fluoride-induced oxidative stress and testicular dysfunction in rats

Objective: To investigate the effect of Camellia (C.) sinensis in mitigating oxidative damage and reproductive toxicity in testis induced by sodium fluoride in a rat model.Methods: Twenty-four adult male Wister rats were divided into 4 groups, with 6 rats in each group. Group 1 orally received distilled water (1 mL/100 g body weight) daily and served as the control group, while group 2 received drinking water with 100 ppm sodium fluoride per day for 21 consecutive days, group 3 was administered with only C. sinensis extract by gavage at a dose of 100 mg/kg body weight and group 4 received drinking water with 100 ppm sodium fluoride and 100 mg/kg body weight C. sinensis leaf extract per day for 21 consecutive days. At the end of the treatment, the rats were sacrificed under light ether anesthesia. The gonado-somatic index, sperm count and motility, serum level of luteinizing hormone and testosterone were assayed. Lipid peroxidation [malondialdehyde (MDA) level], nitric oxide (NO) production, and activities of antioxidant enzymes - superoxide dismutase (SOD), catalase, and reduced glutathione level (GSH) were also analysed. Results: Sodium fluoride treatment significantly decreased gonado-somatic index, sperm count and motility as well as the serum level of luteinizing hormone and testosterone (P<0.05). The histological examination of testes revealed atrophy and degenerative changes in several seminiferous tubules, along with enhanced interstitial space and a reduced number of Leydig cells. There was a highly significant increase in NO and MDA production (P<0.05), while SOD, catalase activities and GSH level decreased significantly (P<0.05). However, C. sinensis significantly restored testicular weight, sperm parameter, hormonal level (P<0.05), and also reversed MDA and NO generation and antioxidant enzymes activities in the testicular tissue (P<0.05).Conclusions: C. sinensis may have an ameliorative role against sodium fluoride-induced oxidative damage in the testis probably because of its antioxidant property.

Effect of Ginkgo biloba extract on Hematological and Biochemical alterations in Fluoride intoxicated Wistar rats

Objective: The present study was aimed to evaluate the potentials of Ginkgo biloba extract against fluoride toxicity by measuring the hematological and biochemical variables in Wistar rats. Methods: Thirty male adult Wistar rats were randomly separated into 5 Groups (n=6 in each Group). Group 1 (Control) received filtered water, 2 to 5 Groups were treated with 100 ppm of sodium fluoride for 30 days, while the Groups 3, 4, and 5 were Ginkgo biloba extract treated at 50 mg/kg, 100mg/kg and 200 mg/kg body weight for 15 days, after sodium fluoride treatment. Results: Administration of fluoride resulted in significant decrease in the red blood cells (RBC), haemoglobin (Hb), packed cell volume (PCV), white blood cells (WBC), platelets count (PLT) in blood and total protein and albumin levels in serum of fluoride group as compared to control group, whereas significant increase in the biochemical parameters such as cholesterol, alanine amino transferase (ALT), aspartate amino transferase (AST) and alkaline phosphatase (ALP) were seen in fluoride group in comparison with control group. Supplementation of Ginkgo biloba extract (GBE) to fluoride intoxicated rats significantly attenuated hematological and biochemical parameters in a dose dependant manner. Conclusion: Ginkgo biloba extract has dose dependant protective effect on fluoride induced hematological and biochemical toxicity and holds potentials for the treatment of fluoride toxicity.

Studies on effects of sodium fluoride on seed germination and plant growth of Rauvolfia Tetraphylla L. a medicinally important plant

Plants are an indispensable source of various needs of human beings such as food, construction tools, flavoring agents, and medicine. Rauvolfia tetraphylla L. is endangered and is one of the important plants of Apocynaceae family being cultivated for its immense medicinal properties. The present studies on Fluoride contamination in water, soil and plants is a serious health problem throughout the world. We studied the effect of aqueous solutions of 0, 0.5, 1.0, 1.5, 2.0, 2.5 and 3.0 mM Sodium fluoride on seed germination and seedling growth of R. tetraphylla at the end of Two months of treatment. Significant reduction in root length, shoot length, Leaf legnth, fresh weight, % of germination were observed at increasing fluoride concentration. Decreasing trend in the growth of roots were observed with increasing Sodium Fluoride concentrations. The percentage of seedling growth decreased up to 62 percent with increasing Sodium fluoride treatment At 0.02 M Sodium Fluoride, significantly reduced growth in the root and shoot lengths occurred in all the seedlings, except the root lengths. In general, the shoot growth was more affected than the root growth at higher concentrations of Sodium Fluoride. The plants growth in soil supplemented with 400 mg NaF/kg soil shows maximum reduction in their growth parameters as compared to control plants.

Aberrant methylation-induced dysfunction of p16 is associated with osteoblast activation caused by fluoride.

Chronic exposure to fluoride continues to be a public health problem worldwide, affecting thousands of people. Fluoride can cause abnormal proliferation and activation of osteoblast and osteoclast, leading to skeletal fluorosis that can cause pain and harm to joints and bones and even lead to permanent disability. Nevertheless, there is no recognized mechanism to explain the bone lesions of fluorosis. In this work, we performed a population study and in vitro experiments to investigate the pathogenic mechanism of skeletal fluorosis in relation to methylation of the promoter of p16. The protein coded by the p16 gene inhibits cdk (cyclin-dependent kinase) 4/cdk6-mediated phosphorylation4 of retinoblastoma gene product and induces cell cycle arrest. The results showed that hypermethylation of p16 and reduced gene expression was evident in peripheral blood mononuclear cells of patients with fluorosis and correlated with the level of fluoride exposure. Studies with cell cultures of osteoblasts revealed in response to sodium fluoride (NaF) treatment, there was an induction of p16 hypermethylation and decreased expression, leading to increased cell proliferation, a longer S-phase of the cell cycle, and development of skeletal fluorosis. Further, the methylation inhibitor, 5-aza-2-deoxycytidine, reversed the p16 hypermethylation and expression in response to NaF. These results reveal a regulatory role of p16 gene methylation on osteoblasts activation during the development of skeletal fluorosis.

Amelioration of the Protein Expression of Cox2, NFκB, and STAT-3 by Some Antioxidants in the Liver of Sodium Fluoride-Intoxicated Rats.

The present study aimed to explore the efficiency of N-acetyl cysteine (NACC) or thymoquinone (TMQ) alone or in combination in the downregulation of inflammatory molecule expression and decreasing hepatic injury in response to sodium fluoride (SF). Sodium fluoride upregulated serum alanine and aspartate transferases activities, tumor necrosis factor α and hepatic malondialdehyde and nitric oxide levels, and the expression of cyclooxygenase 2, nuclear factor κB cell, and signal transducer and activator of transcription 3. In contrast, hepatic glutathione level, superoxide dismutase activity, and nuclear factor erythroid 2-related factor 2 expression were decreased. However, the concurrent treatment with antioxidants, alone or in combination, modulated the levels of these parameters. Histopathological examination revealed that SF treatment resulted in focal areas of massive hepatic degeneration and many degenerated hepatocytes, whereas the treatment with TMQ or NACC exhibited moderate improvement in cellular degeneration of the liver with many abnormal cells. Rats receiving a combination of TMQ and NACC showed marked improvement in cellular degeneration of liver with apparently normal hepatic architecture with very few degenerated hepatocytes. The results also revealed that the combination of TMQ and NACC is the most effective regimen in ameliorating SF toxicity, suggesting their efficacy against the toxicity of fluoride compounds. Their activities might be mediated via multiple molecular pathways.

Fluoride induces DNA damage and cytotoxicity in human hepatocellular carcinoma cells

ABSTRACTHumans are primarily exposed to fluoride (Fl), a widespread environmental pollutant, via contaminated drinking water and foodstuffs. The aim of this study was to examine whether sodium fluoride (NaF) exerted cytotoxic effects in human hepatocarcinoma (HepG2) cells. HepG2 cells were incubated with different concentrations of NaF and reactive oxygen species (ROS) levels, cell cycle, apoptosis, and DNA damage determined. Concentration-dependent studies showed that exposure to HepG2 cells with different concentrations of NaF for 24 hr significantly decreased cell viability and intracellular antioxidant capacity. Furthermore, NaF exposure increased lipid peroxidation levels and accumulation of intracellular ROS; and lowered antioxidant glutathione concentrations. In addition to oxidative impairments, NaF treatment enhanced HepG2 cell death via apoptotic pathway as evidenced by DNA fragmentation and cell cycle arrest. Sodium fluoride treatment unregulated p53 level, and Bax and Bcl2 expression. Diminished cell viability and changes in cell cycle accompanied a rise in p53 expression.

Effect of Sodium Fluoride on Seed Germination, Seedling Growth and Biochemistry of Abelmoschus esculentus

Fluoride contamination in water, soil and plants is a serious health problem throughout the world. We studied the effect of aqueous solutions of 0, 10, 20, 30, 40 and 50 ppm sodium fluoride on seed germination, seedling growth and biochemical parameters of Abelmoschus esculentus. The experiment was conducted as factorial with completely randomized design with five replicates. The percentage of seed germination decreased up to 62 percent with increasing sodium fluoride treatment. The seedling growth parameters (root length, shoot length and vigor index) and biochemical parameters i.e., chlorophyll, nitrogen and protein content as well as the Fluoride uptake by the germinated seedlings were estimated after 20 days of treatment.

Effects of sodium fluoride treatment in vitro on cell proliferation, BMP-2 and BMP-3 expression in human osteosarcoma MG-63 cells.

Chronic excessive fluoride intake may cause fluorosis, which chiefly manifests as bone damage (or skeletal fluorosis). However, the molecular mechanism of skeletal fluorosis has not been clarified up to the present. The objective of this study was to analyze the effects of fluoride treatment on two of bone morphogenetic protein family member (BMP-2 and BMP-3) expression and cell viability using human osteosarcoma MG-63 cells as a model. Sodium fluoride (NaF) had pro-proliferation effects at relatively moderate concentration, with 5 × 10(3) μmol/L having the best effects. At 2 × 10(4) μmol/L, NaF inhibits cell proliferation. BMP-2 and BMP-3 expression was significantly induced by 5 × 10(3) μmol/L NaF and, to lesser extent, by 2 × 10(4) μmol/L NaF. Correspondingly, mothers against decapentaplegic homolog 1 (Smad-1) increased at both doses of NaF, which indicated the BMP signaling pathway was activated. Notable increases in secreted alkaline phosphatase (ALP) were observed when cells were treated with 5 × 10(3) μmol/L NaF. A BMP specific inhibitor LDN193189 suppressed cell proliferation induced by 5 × 10(3) μmol/L NaF. Also, 2 × 10(4) μmol/L NaF induced apoptosis but likely through a mechanism unrelated to the BMP pathway. Collectively, data show that NaF had dose-dependent effects on cell proliferation as well as BMP-2 and BMP-3 expression in MG-63 cells and suggested that cell proliferation enhanced by NaF-induced BMP members may be a molecular mechanism underlying skeletal fluorosis.

Limited evidence for the effect of sodium fluoride on deterioration of hearing loss in patients with otosclerosis: a systematic review of the literature.

To determine the protective effect of sodium fluoride on the deterioration of hearing loss in adult patients with otosclerosis. PubMed, Embase, the Cochrane Library, and CINAHL. A systematic literature search was conducted. Studies reporting original study data on the deterioration of hearing loss in otosclerosis patients treated with sodium fluoride were included. Directness of evidence (DoE) and risk of bias (RoB), using the Cochrane Collaboration's tool for assessing risk of bias, of the selected articles were assessed. Studies with low DoE, high RoB, or both were excluded. Absolute risks, mean deterioration of hearing in decibels, risk differences, and their 95% confidence intervals were extracted from the included studies. Our search yielded 168 original titles, of which, 2 placebo-controlled studies were eligible for data extraction. The results of these 2 studies were conflicting. One of the included studies, with high DoE and moderate RoB, reported an absolute risk reduction for deterioration of hearing loss of 18% [95% CI 17; 19] when treating with sodium fluoride. The other included study, with high DoE and moderate RoB, reported no clinically significant difference in mean deterioration of bone-conduction, air-conduction, or air-bone gap between the sodium fluoride group and the placebo group. There is weak evidence from one study with significant limitations that deterioration of hearing loss in otosclerosis patients receiving sodium fluoride treatment is less than in patients treated with a placebo.

Structural alterations in compound eye of Drosophila melanogaster in response to sodium fluoride treatment

Sodium fluoride, used as a pesticide in agriculture, is also an ingredient of toothpastes which help to fight dental problems. In this study, Drosophila melanogaster, a non-target organism, is used to explore morphological changes in the adult compound eye as a function of exposure to fluoride at 20, 40, 80, 100 and 150 mg L−1, using scanning electron microscopy. The experimental concentrations were much lower than the ones used in the studies of the British Association of Community Dentistry. Distinct morphological alterations in the eye of the treated insects revealed ommatidial ridges and disoriented mechanosensory bristles which were most prominent in the 40 and 80 mg L−1 treatment groups. Since humans and Drosophila share homology in many genes that are involved in developmental pathways, the present findings raise concern on the use of sodium fluoride as a pesticide.