Tamarind seed coat ameliorates fluoride induced cytotoxicity, oxidative stress, mitochondrial dysfunction and apoptosis in A549 cells.

Fluoride (F) is an environmental contaminant and industrial pollutant. Molecular mechanisms remain unclear in F induced pulmonary toxicity even after numerous studies. Tamarind fruits act as defluoridating agents, but no study was conducted in in vitro systems. Hence, we aimed to assess the ameliorative impact of the tamarind seed coat extract (TSCE) against F toxicity utilizing lung epithelial cells, A549. Cells were exposed to sodium fluoride (NaF-5 mM) alone and in combination with TSCE (750 ng/ml) or Vitamin C (positive control) for 24 h and analyzed for F content, intracellular calcium ([Ca(2+)]i) level, oxidative stress, mitochondrial integrity and apoptotic markers. TSCE treatment prevented the F induced alterations in [Ca(2+)]i overload, F content, oxidant (reactive oxygen species generation, lipid peroxidation, protein carbonyl content and nitric oxide) and antioxidant (superoxide dismutase, catalase, glutathione peroxidase and glutathione) parameters. Further, TSCE modulates F activated changes in mitochondrial membrane potential, permeability transition pore opening, cytochrome-C release, Bax/Bcl-2 ratio, caspase-3 and PARP-1 expressions. In conclusion, our study demonstrated that TSCE as a potential protective agent against F toxicity, which can be utilized as a neutraceutical.

Single oral acute fluoride exposure causes changes in cardiac expression of oxidant and antioxidant enzymes, apoptotic and necrotic markers in male rats.

Several studies have shown that acute fluoride (F(-)) exposure impairs cardiac function, but the molecular mechanism is not clear. In order to study this, male Wistar rats were treated with single oral doses of 45 and 90 mg/kg F(-) for 24 h. A significant accumulation of F(-) was found in the serum and myocardium of experimental rats. F(-) treatment causes myocardial necrosis as evident from increased levels of myocardial troponin I, creatine kinase, lactate dehydrogenase and aspartate transaminase. In addition, F(-) induces myocardial oxidative stress via increased reactive oxygen species, lipid peroxidation, protein carbonyl content and nitrate levels along with decreased in the levels of enzymatic (superoxide dismutase 2, catalase, glutathione peroxidase and glutathione s transferase pi class) and non-enzymatic (reduced glutathione) antioxidants. Notably, F(-) triggers myocardial apoptosis through altered Bax/Bcl2 ratio and increased cytochrome c, caspase 3p20 and terminal deoxynucleotidyl transferase dUTP nick end labeled positive cells. An increased cardiac expression of Nox4 and p38α MAPK in F(-) treated rats indicates the oxidative and apoptotic damage. Moreover, ultra-structural changes, histopathological and luxol fast blue staining demonstrates the degree of myocardial damage at subcellular level. Taken together, these findings reveal that acute F(-) exposure causes cardiac impairment by altering the expression of oxidative stress, apoptosis and necrotic markers.

Vitamin A deficiency: An oxidative stress marker in sodium fluoride (NaF) induced oxidative damage in developing rat brain.

Fluoride induced oxidative stress through depletion in levels of various anti-oxidants such as glutathione, superoxide dismutase (SOD), fat soluble vitamins (D and E) with increased levels of lipid peroxidation (LPO) and fluoride aggravate the damage in rodents as well as in humans. Vitamins A, a fat soluble vitamin possess antioxidant property which plays a significant role in scavenging the free radicals species similar to vitamin D and E. Vitamin A is involved in neural tissue development and plasticity. The growing evidence about vitamin A being antioxidant in different biological reactions formed the basis to determine the effect of fluoride on its levels. The present study was conducted in Wistar rat pups. The pregnant wistar rats were dosed with 20 ppm sodium fluoride (NaF) from day one of pregnancy till the pups were aged day 30. The serum was collected from developing rat pups on regular intervals (14th, 21st, 30th day) and vitamin A levels were analyzed by High performance liquid chromatography (HPLC). Body weights, Behavioural studies and spectrophotometric estimation of SOD, LPO in brain lysates were also performed. The results showed significant decrease (p<0.001) in vitamin A in fluoride induced samples in comparison to the control samples suggesting that decreased levels of vitamin A can be used as another marker in fluoride induced toxicity studies.

Fluoride Modulates Parathyroid Hormone Secretion in vivo and in vitro.

The study objective was to investigate the effects of fluoride on intact parathyroid hormone (iPTH) secretion. Thyro-parathyroid complexes (TPC) from C3H (n = 18) and B6 (n = 18) mice were cultured in Ca²âº-optimized medium. TPC were treated with 0, 250, or 500 µM NaF for 24 h and secreted iPTH assayed by ELISA. C3H (n = 78) and B6 (n = 78) mice were gavaged once with distilled or fluoride (0.001 mg [F⁻]/g of body weight) water. At serial time points (0.5-96 h) serum iPTH, fluoride, total calcium, phosphorus, and magnesium levels were determined. Expression of genes involved in mineral regulation via the bone-parathyroid-kidney (BPK) axis, such as parathyroid hormone (Pth), calcium-sensing receptor (Casr), vitamin D receptor (Vdr), parathyroid hormone-like hormone (Pthlh), fibroblast growth factor 23 (Fgf23), α-Klotho (αKlotho), fibroblast growth factor receptor 1c (Fgf1rc), tumor necrosis factor 11 (Tnfs11), parathyroid hormone receptor 1 (Pth1r), solute carrier family 34 member 1 (Slc34a1), solute carrier 9 member 3 regulator 1 (Slc9a3r1), chloride channel 5 (Clcn5), and PDZ domain-containing 1 (Pdzk1), was determined in TPC, humeri, and kidneys at 24 h. An in vitro decrease in iPTH was seen in C3H and B6 TPC at 500 µM (p < 0.001). In vivo levels of serum fluoride peaked at 0.5 h in both C3H (p = 0.002) and B6 (p = 0.01). In C3H, iPTH decreased at 24 h (p < 0.0001), returning to baseline at 48 h. In B6, iPTH increased at 12 h (p < 0.001), returning to baseline at 24 h. Serum total calcium, phosphorus, and magnesium levels did not change significantly. Pth, Casr,αKlotho,Fgf1rc,Vdr, and Pthlh were significantly upregulated in C3H TPC compared to B6. In conclusion, the effects of fluoride on TPC in vitro were equivalent between the 2 mouse strains. However, fluoride demonstrated an early strain-dependent effect on iPTH secretion in vivo. Both strains demonstrated differences in the expression of genes involved in the BPK axis, suggesting a possible role in the physiologic handling of fluoride.

Impact of Personal Characteristics and Technical Factors on Quantification of Sodium 18F-Fluoride Uptake in Human Arteries: Prospective Evaluation of Healthy Subjects.

UNLABELLED: Sodium 18F-fluoride (18F-NaF) PET/CT imaging is a promising imaging technique for the assessment of atherosclerosis but is hampered by a lack of validated quantification protocols. Both personal characteristics and technical factors can affect quantification of arterial 18F-NaF uptake. This study investigated whether blood activity, renal function, injected dose, circulating time, and PET/CT system affect quantification of arterial 18F-NaF uptake. METHODS: Eighty-nine healthy subjects were prospectively examined by 18F-NaF PET/CT imaging. Arterial 18F-NaF uptake was quantified at the level of the ascending aorta, aortic arch, descending thoracic aorta, and coronary arteries by calculating the maximum 18F-NaF activity (NaFmax), the maximum/mean target-to-background ratio (TBRmax/mean), and the maximum blood-subtracted 18F-NaF activity (bsNaFmax). Multivariable linear regression assessed the effect of personal characteristics and technical factors on quantification of arterial 18F-NaF uptake. RESULTS: NaFmax and TBRmax/mean were dependent on blood activity (ß=0.34 to 0.44, P<0.001, and ß=-0.68 to -0.58, P<0.001, respectively) and PET/CT system (ß=-0.80 to -0.53, P<0.001, and ß=-0.80 to -0.23, P<0.031, respectively). bsNaFmax depended on PET/CT system (ß=-0.91 to -0.57, P<0.001) but not blood activity. This finding was observed at the level of the ascending aorta, aortic arch, descending thoracic aorta, and the coronary arteries. In addition to blood activity and PET/CT system, injected dose affected quantification of arterial 18F-NaF uptake, whereas renal function and circulating time did not. CONCLUSION: The prospective evaluation of 89 healthy subjects demonstrated that quantification of arterial 18F-NaF uptake is affected by blood activity, injected dose, and PET/CT system. Therefore, blood activity, injected dose, and PET/CT system should be considered to generate accurate estimates of arterial 18F-NaF uptake.

Comparison of the Biological Impacts of the Fluoride Compounds by Graphical Risk Visualization Map Technique.

Various fluoride compounds are widely used in industry. The present risk assessment study was conducted using a series of inorganic binary fluorides of the type XFn, where X(n) = Na(+), K(+), Li(+), Mg(2+), Ca(2+), Sr(2+), Ba(2+), Al(3+), Nd(3+), La(3+), Ce(3+), Sm(3+), Gd(3+), Y(3+), Yb(2+), and Zn(2+). The aqueous solutions of these salts were orally administrated to 16 experimental groups (one for each of the salts tested). The levels of fluoride, N-acetyl-ß-D-glucosaminidase in cumulative 24-h urine samples and creatinine clearance were measured to assess possible acute renal damages. The levels of fluoride, alanine aminotransferase, and aspartate aminotransferase were also determined in serum samples to assess possible acute hepatic damages. The results reveal that sodium fluoride (NaF), potassium fluoride (KF), and zinc fluoride tetrahydrate (ZnF2 (.)4H2O) can carry the fluoride ion into the bloodstream and that it is excreted via urine more readily than the other compounds tested. These fluorides were assigned the highest risk impact factor. Most of the rare earth fluorides are insoluble in water while those groups 2 and 13 of the periodic table are slightly soluble, so that they do not have a significant negative risk. These findings suggest that the biological impact of fluoride depends on the accompanying counter ion and its solubility. The risk map obtained in the present study shows that the graphical visualization map technique employed is a valuable new tool to assess the toxicological risk of chemical compounds.

High concentration aqueous sodium fluoride certified reference materials for forensic use certified by complexometric titration.

Sodium fluoride in concentrations of 1 to 2 % is used to prevent the formation of ethanol in blood and urine samples that are to be analysed for ethanol content. The majority of such samples form part of forensic investigations into alleged drunken driving. In South Africa, the laboratory performing the tests is required to prove that the sodium fluoride concentration in the blood samples is above 1 g/100 ml on receipt. This is done by using a fluoride ion-selective electrode calibrated with external aqueous solutions of sodium fluoride. The National Metrology Institute of South Africa (NMISA) prepares sodium fluoride solutions in concentrations from 0.3 to 3.0 g/100 ml. No other certified sodium fluoride reference solutions in these concentrations are available commercially. The sodium fluoride is certified by precipitation of the fluoride as lead chlorofluoride (PbClF) through the addition of a known excess of lead nitrate. The excess lead is back-titrated with ethylenediamine tetraacetic acid (EDTA) using a photometric electrode to detect the endpoint. Aqueous sodium fluoride solutions are prepared and the concentrations verified by the precipitation/back-titration method. This paper shows the application of a classical complexometric method to the certification of reference materials and describes the procedures for the preparation of the sodium fluoride solutions, verification of the concentrations, homogeneity and stability by primary titrimetry. It also briefly covers the calculation of uncertainty, the establishment of traceability and the quality control measures applied to ensure the quality of the certified reference materials (CRMs).

Evaluation of the Analytical Performance of the Olympus AU5421 Applied with Parameters Developed by the Toshiba 200FR for Measurement of Blood Ethanol Concentration.

BACKGROUND: An accurate determination of blood ethanol concentrations is important. To minimize ethanol degradation in blood samples, sodium fluoride (NaF) collection tubes have been recommended for use. In this study, we attempted to utilize the Olympus AU5421 chemistry analyzer for ethanol analysis based on the parameters established for the Toshiba 200FR. We also evaluated the effect of NaF collection tubes on ethanol concentrations. METHODS: The precision, linearity, accuracy, and carry-over rate of the AU5421 analyzer were evaluated. The results of analysis using the AU5421 and Abbott AxSYM analyzers were also compared. The effects of NaF collection tubes on ethanol concentrations in stored samples were measured. RESULTS: The AU5421 showed a good precision, linearity, accuracy, and carry-over rate. The ethanol concentrations were well correlated with the results obtained using the AxSYM. There was no statistically significant difference in blood ethanol concentrations between the samples collected in tubes with NaF and those collected in tubes without NaF. CONCLUSIONS: Since the AU5421 showed excellent analytical performance, the AU5421 could be used as an alternative to AxSYM for the determination of blood ethanol concentrations. Our analysis also indicated that there is no need to use NaF collection tubes if blood ethanol concentrations are analyzed within 3 h after blood collection. We believe that the results obtained in this study will have important implications for the use of the AU5421 system to measure blood ethanol concentrations.

Pharmacokinetics of fluoride in toddlers after application of 5% sodium fluoride dental varnish.

The prevalence of dental caries (tooth decay) among preschool children is increasing, driven partially by an earlier age of onset of carious lesions. The American Academy of Pediatrics recommends application of 5% sodium fluoride varnish at intervals increasing with caries risk status, as soon as teeth are present. However, the varnishes are marketed for treatment of tooth sensitivity and are regulated as medical devices rather than approved by the US Food and Drug Administration for prevention of dental caries (tooth decay). The objective of this research is to examine the safety of use in toddlers by characterizing the absorption and distribution profile of a currently marketed fluoride varnish. We measured urinary fluoride for 5 hours after application of fluoride varnish to teeth in 6 toddlers aged 12 to 15 months. Baseline levels were measured on a separate day. The urine was extracted from disposable diapers, measured by rapid diffusion, and extrapolated to plasma levels. The mean estimated plasma fluoride concentration was 13 µg/L (SD, 9 µg/L) during the baseline visit and 21 µg/L (SD, 8 µg/L) during the 5 hours after treatment. Mean estimated peak plasma fluoride after treatment was 57 µg/L (SD, 22 µg/L), and 20 µg/kg (SD, 4 µg/L) was retained on average. Retained fluoride was 253 times lower than the acute toxic dose of 5 mg/kg. Mean plasma fluoride after placement of varnish was within an SD of control levels. Occasional application of fluoride varnish following American Academy of Pediatrics guidance is safe for toddlers.

Fluoride and arsenic exposure impairs learning and memory and decreases mGluR5 expression in the hippocampus and cortex in rats.

Fluoride and arsenic are two common inorganic contaminants in drinking water that are associated with impairment in child development and retarded intelligence. The present study was conducted to explore the effects on spatial learning, memory, glutamate levels, and group I metabotropic glutamate receptors (mGluRs) expression in the hippocampus and cortex after subchronic exposure to fluoride, arsenic, and a fluoride and arsenic combination in rats. Weaned male Sprague-Dawley rats were assigned to four groups. The control rats drank tap water. Rats in the three exposure groups drank water with sodium fluoride (120 mg/L), sodium arsenite (70 mg/L), and a sodium fluoride (120 mg/L) and sodium arsenite (70 mg/L) combination for 3 months. Spatial learning and memory was measured in Morris water maze. mGluR1 and mGluR5 mRNA and protein expression in the hippocampus and cortex was detected using RT-PCR and Western blot, respectively. Compared with controls, learning and memory ability declined in rats that were exposed to fluoride and arsenic both alone and combined. Combined fluoride and arsenic exposure did not have a more pronounced effect on spatial learning and memory compared with arsenic and fluoride exposure alone. Compared with controls, glutamate levels decreased in the hippocampus and cortex of rats exposed to fluoride and combined fluoride and arsenic, and in cortex of arsenic-exposed rats. mGluR5 mRNA and protein expressions in the hippocampus and mGluR5 protein expression in the cortex decreased in rats exposed to arsenic alone. Interestingly, compared with fluoride and arsenic exposure alone, fluoride and arsenic combination decreased mGluR5 mRNA expression in the cortex and protein expression in the hippocampus, suggesting a synergistic effect of fluoride and arsenic. These data indicate that fluoride and arsenic, either alone or combined, can decrease learning and memory ability in rats. The mechanism may be associated with changes of glutamate level and mGluR5 expression in cortex and hippocampus.

The effect of chronic treatment with fluoride on salivary activity, tooth, and bone in spontaneously hypertensive rats (SHR).

The present study evaluated the effect of chronic treatment with sodium fluoride on salivary activity, tooth, and bone in spontaneously hypertensive rats (SHR). The treatment was made with a 20-ppm NaF solution added to the drinking water for 30 days. Systolic blood pressure values were obtained by plethysmography; fluoride concentration was determined by an ion-selective electrode; calcium concentration and amylase activity were determined by commercial kits; and enamel microhardness was verified by longitudinal section. Systolic blood pressure values and animals' weight were not changed by treatment. However, the salivary flow rate-which was lowered in SHR at baseline when compared to Wistar rats-was found to be increased with the treatment with NaF. The fluoride concentration was increased in the plasma of the treated groups, even though it remained lower for the treated SHR in relation to the treated Wistar rats. Calcium concentration was decreased in the saliva and plasma of SHR treated with NaF. A reduction in the plasmatic total protein concentration was observed in SHR treated with NaF. The fluoride concentration on bone surface was found to be increased in Wistar or SHR treated with NaF. In treated SHR's femurs, it was observed a significant reduction in fluoride concentrations. Enamel microhardness of the incisor teeth was not changed by the treatment with NaF in both groups. The distribution of fluoride to the salivary glands in SHR is poor, and treatment with NaF causes a decrease in the concentration of important biochemical parameters to the salivary physiology in SHR.

The toxicity mechanism of sodium fluoride on fertility in female rats.

Recognition of the harmful effects of sodium fluoride (NaF) on human reproduction is increasing, especially as it relates to female reproduction. However, the mechanism by which NaF interferes with female reproduction is unclear. The aims of the present study were to investigate the effects of fluoride exposure on female fertility and to elucidate the mechanisms underlying these effects. Female Sprague-Dawley rats were divided into three groups: one control group and two NaF-treated groups (100 and 200 mg/L in the drinking water for 12 weeks). Several parameters were evaluated, including: (i) fluoride concentrations; (ii) estrogen (E2) and progesterone (P) concentrations; (iii) estrogen receptor alpha protein (ERα); (iv) progesterone receptor (PgR) protein; (v) follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR) protein. The results indicated that administration of NaF lead to significant decreases in E2 and P levels in the serum and in the expression of FSHR protein. In addition, fluoride exposure significantly increased Erα and PgR protein expression levels and LHR protein expression. These results suggest that the reproductive hormone reduction and the abnormalities of related receptor proteins expression are important factors underlying the decreased fertility observed in female rats that have been exposed to NaF.

Physical exercise ameliorates the toxic effect of fluoride on the insulin-glucose system.

Daily intake of water with fluoride concentrations >1.5 mg/l produces insulin resistance (IR). On the other hand, physical activity increases insulin sensitivity in the muscle. Therefore, the aim of this study was to evaluate the effect of physical activity on IR in rats treated with sodium fluoride (NaF) in drinking water. Sprague-Dawley rats were divided into three groups (n=10/group): Control (drinking water without NaF), NaF (drinking water with NaF 15 mg/l for 30 days), and Exercise (daily running on a treadmill for 60 min at 2.25 m/min and drinking water with NaF 15 mg/l for 30 days). IR was evaluated with the homeostasis model assessment-IR (HOMA-IR) index using fasting plasma levels of glucose and insulin. IR increased in rats treated with 15 mg/l NaF in drinking water. A decrease in IR was observed in rats that performed physical activity and drank water with 15 mg/l NaF; the Exercise group also showed an increase in the amounts of bone fluoride. The variation in the HOMA-IR values could be the consequence of variation in the sensitivity of tissues to insulin or decrease in plasma fluoride levels due to bone fluoride intake. These findings indicate that the performance of daily physical activity could reduce the negative effects of the chronic ingestion of NaF on glucose homeostasis.

Assessment of blood pool, soft tissue, and skeletal uptake of sodium fluoride F 18 with positron emission tomography-computed tomography in four clinically normal dogs.

OBJECTIVE: To determine the ideal interval to image acquisition after IV injection of sodium fluoride F 18 ((18)F-NaF) and evaluate biodistribution of the radiopharmaceutical in clinically normal skeletally immature dogs. ANIMALS: 4 female dogs. PROCEDURES: Each dog was anesthetized for evaluation with a commercial hybrid positron emission tomography (PET)-CT instrument. A low-radiation dose, whole-body CT scan was acquired first. An IV injection of (18)F-NaF (0.14 mCi/kg) was administered, and a dynamic PET scan centered over the heart and liver was acquired during a period of 120 minutes. Uptake of (18)F-NaF in the blood pool, soft tissues, and skeletal structures was evaluated via region of interest analysis to derive standardized uptake values and time-activity curves, which were used to determine the optimal postinjection time for skeletal image acquisition. Biodistribution was also assessed from a final whole-body PET-CT scan acquired after the dynamic scan. RESULTS: Time-activity curves revealed a rapid decrease in the amount of radiopharmaceutical in the blood pool and soft tissues and a rapid increase in the amount of radiopharmaceutical in bones soon after injection. At 50 minutes after injection, the greatest difference in uptake between soft tissues and bones was detected, with continued subtle increase in uptake in the bones. Uptake of (18)F-NaF was slightly increased at growth plates and open ossification centers, compared with that at other parts of the bone. CONCLUSIONS AND CLINICAL RELEVANCE: At 50 minutes after IV injection of (18)F-NaF at the dose evaluated, PET-CT yielded excellent bone-to-background ratio images for evaluation of the skeletal system in dogs.

Ameliorative effect of tamarind leaf on fluoride-induced metabolic alterations.

OBJECTIVES: Fluoride is a serious health hazard across several nations, and chronic intake of fluoride deranges the carbohydrate, lipid and antioxidant metabolism in general. As there are limited remedial measures to prevent fluorosis, we investigated the role of tamarind leaf as a food supplement in restoration of carbohydrate, lipid and antioxidant metabolism in fluoride-exposed albino rats. METHODS: Albino rats were exposed to fluoride (100 ppm sodium fluoride) through drinking water and fed diet supplemented with tamarind leaf powder (2.5, 5 and 10 g %) for 4 weeks. Carbohydrate, lipid and antioxidant profiles were investigated in both controls and fluoride-exposed animals. RESULTS: While 4-week exposure to fluoride elevated plasma glucose and lipid profiles, simulating diabetic and hyperlipidaemic conditions, the antioxidant defence mechanisms of fluoride-exposed rats were compromised, with elevation and decline in lipid peroxidation and high-density lipoprotein (HDL)-cholesterol, respectively. When the diet was supplemented with tender tamarind leaves (used in southern India as a replacement for tamarind or other sour food ingredients), significant improvements in carbohydrate and lipid profiles occurred as evidenced by decreased plasma glucose and lipid levels, lipid peroxidation, increased hepatic glycogen content, hexokinase activity and cholesterol excretion, with simultaneous improvement in antioxidant profiles of both hepatic and renal tissues. CONCLUSIONS: These findings are significant in view of the need for cost-effective approaches to tackle fluorosis as an environmental hazard and use of food supplements as ameliorative measures.

Effect of fluoride exposure on bone metabolism indicators ALP, BALP, and BGP.

OBJECTIVE: To analyze the changes in serum alkaline phosphatase (ALP) and bone alkaline phosphatase (BALP) activity and changes in osteocalcin (BGP) content following fluoride exposure and, thereby, determine the reference indications of fluoride-induced changes in bone metabolism. METHODS: In the animal study, rats were allowed free access to drinking water containing different concentrations (10, 150, or 400 mg/L) of sodium fluoride. Serum ALP and BALP activity and serum BGP content were assessed at three exposure time-points. In the spot study, serum ALP and BALP activity and serum BGP content were assessed in workers exposed to fluoride in their working environment for different periods of time. RESULTS: Compared with the control group, on days 15 and 30, the activity of serum ALP in the low- and medium-dose group was significantly higher (p < 0.05), while in the high-dose group it was significantly lower (p < 0.05). Only on day 30 was the activity of serum BALP in the medium-dose group significantly higher than that of the control group (p < 0.05). BGP content was lower in the high-dose group than in the control group (p < 0.05) on days 30 and 90, but it was higher in the medium-dose group on day 90. Compared with the control group, BGP content in the fluoride-exposed group was higher (p < 0.05). In the spot study, serum ALP activity and serum BGP content in the medium working-age group were higher than that in the short working-age group (p < 0.05). However, serum ALP activity and serum BGP content were lower in the long working-age group than in the medium working-age group (p < 0.05). CONCLUSIONS: Our results suggest that serum fluoride and urinary fluoride can be used as reference indications to provide an overall reflection of the body's fluoride-load and fluoride exposure level. Serum ALP activity and serum BGP content can be used as important reference indications for diagnosing bone metabolism changes resulting from fluoride exposure.

In vivo efficacy of tamarind (Tamarindus indica) fruit extract on experimental fluoride exposure in rats.

The study was undertaken to determine the efficacy of hydro-methanolic (1:1) extract of tamarind (Tamarindus indica L.) fruit pulp in removing body fluoride burden. Thirty rats were divided into five groups. Keeping no fluoride group as the control, rats of no treatment, low dose, middle dose and high dose groups received sodium fluoride orally at the rate of 200mg per kg body weight daily for 14 weeks. Rats of low dose, middle dose and high dose group simultaneously received tamarind fruit pulp extract at three doses, viz. 25 (low), 50 (medium) and 100mg (high) per kg body weight orally, respectively. Fluoride concentration in blood, urine and long bone of experimental rats was monitored to assess the efficacy of the extract. Mean serum fluoride concentration in fluoride exposed rats was 0.145 ± 0.009 and 0.783 ± 0.042 µg/ml on days 0 and 98. In comparison, fluoride concentrations in tamarind treated rats were 0.179 ± 0.021 and 0.633 ± 0.015; 0.179 ± 0.021 and 0.502 ± 0.025 and 0.176 ± 0.021 and 0.498 ± 0.030 µg/ml in low, medium and high dose groups, respectively on day 0 and day 98 of the experiment. There was a significant (p ≤ 0.01) increase in urinary fluoride excretion from day 28 onwards. The mean fluoride concentration in long bones of treated rats was significantly lower than the values recorded in fluoride exposed rats. These findings suggest that concomitant use of tamarind fruit pulp extract can reduce fluoride concentration in blood and bone and enhanced urinary excretion, indicating the ameliorative potential of fruits of tamarind in fluoride toxicity.

Co-exposure to arsenic and fluoride on oxidative stress, glutathione linked enzymes, biogenic amines and DNA damage in mouse brain.

We studied the effects of combined exposure to arsenic and fluoride on (i) brain biogenic amines, oxidative stress and its correlation with glutathione and linked enzymes; (ii) alterations in the structural integrity of DNA; and (iii) brain and blood arsenic and fluoride levels. Efficacy of alpha-tocopherol in reducing these changes was also determined. Male mice were exposed to sodium meta arsenite (50 ppm) and sodium fluoride (50 ppm) individually and in combination for ten weeks. Animals were given vitamin E supplementation (5 mg/kg, i.m., alternate days) throughout the experiment. Exposure to arsenic and fluoride significantly decreased the levels of brain biogenic amines. However; acetyl cholinesterase (AChE) and monoamine oxidase (MAO) activities showed an increase on fluoride exposure. There was also an increase in reactive oxygen species, thiobarbituric acid reactive species level, glutathione S-transferase and glutathione peroxidase activities and decreased superoxide dismutase activity, GSH:GSSG ratio, glucose 6-phosphate dehydrogenase activity. Combined exposure to these toxicants produced more pronounced effects on AChE, MAO, SOD and catalase activities. Infrared spectra showed less toxicity during combined exposure as the characteristic peaks of cytosine and alpha-helical structure of DNA were observed in normal and arsenic plus fluoride-exposed animals. Vitamin E reduced brain fluoride level and tissue oxidative stress but had no effect on arsenic. Combined exposure to arsenic and fluoride does not necessarily lead to more pronounced toxicity and interestingly exhibit some antagonistic effects. Vitamin E supplementation may be of added value in reverting some of the toxic effects.

Avaliação da influência do fluoreto no reparo ósseo em alvéolo dental de ratos: análise morfométrica e perfil de atividade das MMP-2 e 9 / Evaluation of the fluoride influence in alveolar bone repair in rats: morphometric analysis and MMP-2 activity

O flúor (F), na forma de fluoreto de sódio (NaF), é um elemento presente no cotidiano de quase a totalidade da população brasileira, sendo usado na água de abastecimento (Brasil) e também como terapêutico para osteoporose (comumente na Europa). Assim sendo, é importante o entendimento do efeito do flúor no reparo ósseo. Neste estudo foram utilizados 4 grupos com ratos Wistar de 80 dias (n=200), os quais receberam água de beber contendo 5, 15 e 50 ppm de flúor e água deionizada (grupo controle) durante todo experimento. Esses animais tiveram o incisivo superior direito extraído. Os animais foram eutanasiados O hora, 7, 14, 21 e 30 dias após a extração, sendo coletado sangue (análise da concentração de flúor), a região do alvéolo dental para análise microscópica (análise histológica e morfometria) e extração de proteínas referentes ao reparo ósseo (metaloproteinases de matriz - MMPs 2 e 9). A análise de concentração de flúor no plasma sangüíneo mostrou maior presença desse elemento no grupo tratado com 50 ppm de F nos períodos de 21 e 30 dias. A análise histológica detectou osso neoformado em todos os animais após 30 dias, porém o grupo de 50 ppm de F apresentou menor formação óssea que os outros grupos. A análise morfométrica mostrou um aumento na densidade de volume de osso neoformado, entre 7 e 30 dias, nos grupos controle, 5, 15 e 50 ppm de F, com concomitante diminuição na densidade de volume de tecido conjuntivo e coágulo sangüíneo. A atividade da MMP-2 foi mais acentuada no período inicial, enquanto a MMP-9 teve maior atividade no período final. Concluiu-se que o F, em altas concentrações, pode retardar o reparo alveolar diminuindo a formação de novo tecido ósseo, associado a um atraso na remissão do coágulo.

The fluorine (F), in the sodium fluoride (NaF) form, is an element daily present for most people, being used in water supply (Brazil) and also as therapy for osteoporosis (common in Europe). In such case it is important the understanding of the effect of fluoride in physiologic repair in bone tissue. This study used 4 groups of rats for 80 days (n = 200), which received drinking water containing 5, 15 and 50 ppm of fluoride, and deionized water (control group) throughout experimento These animais had the right upper incisor extracted. The animais were euthanized O hours, 7, 14, 21 and 30 days after extraction, and blood collected (analysis of the concentration of fluorine), the region of the dental alveolus for microscopic exa'mination (histological analysis and morphometry) and extraction of proteins for the bone repair (the matrix metalloproteinases - MMP 2 and 9). The analysis of concentration of fluoride in blood plasma showed greater presence of that element in the group treated with 50 ppm of F in periods of 21 and 30 days. Histological analysis detected neoformed bone in ali animais after 30 days, but the group of 50 ppm F showed lower bone formation than the other groups. Morphometric analysis showed an increase in the volume density of neoformed bone, between 7 and 30 days in control groups, 5, 15 and 50 ppm F, with a concomitant decrease in the volume density of connective tissue and blood dot. The activity of MMP-2 was more pronounced in the initial period, while MMP-9 had higher activity in the 30 days. It was concluded that the F, in high concentrations, may delay the tooth socket repair reducing the formation of new bone tissue, associated with a delay in remission of blood clot.

Pharmacokinetics of ingested fluoride: lack of effect of chemical compound.

UNLABELLED: Fluoride in drinking water may be present from natural sources or added as sodium fluoride (NaF), sodium silicofluoride (Na(2)SiF(6)) or fluorosilicic acid (H(2)SiF(6)). Results from an early study with rats suggested that, when ingested as Na(2)SiF(6), the absorption and excretion of fluoride were greater than when ingested as NaF. OBJECTIVE: The present single-blind, crossover study with 10 adults was done to determine three key pharmacokinetic parameters: the maximum plasma fluoride concentrations (C(max)), the elapsed time to reach the maximum concentrations (T(max)) and the 6-h areas under the time-plasma concentration curves (AUCs) after ingestion of 500 mL of water containing 0.67 or 5.45 mg F/L present naturally or added as NaF or H(2)SiF(6). DESIGN: Blood was collected prior to and at nine time points during 6h after ingestion of the test solutions. Plasma was analysed by electrode after HMDS-facilitated diffusion and the data were analysed for statistically significant differences using repeated measures ANOVA. RESULTS: The C(max), T(max) and AUC values after ingestion of the solutions containing natural fluoride, NaF or H(2)SiF(6) did not differ significantly at either dose level. Further, the T(max) values associated with the 0.67 and 5.45 mg/L solutions did not differ significantly indicating that the absorption, distribution and elimination rates were not affected by the dose size. CONCLUSIONS: Considered together with published reports, the present findings support the conclusion that the major features of fluoride metabolism are not affected differently by the chemical compounds commonly used to fluoridate water nor are they affected by whether the fluoride is present naturally or added artificially.