NaF Administration Research Articles

Keap1/Nrf2 pathway in sodium fluoride-induced cardiac toxicity and the prophylactic role of vitamin C versus platelet-rich plasma.

The present study was conducted to investigate the role of vitamin C versus platelet-rich plasma (PRP) against sodium fluoride (NaF)-induced cardiotoxicity and cell death in rats' myocardium. Previous studies suggest that NaF decreased cellular viability and intracellular antioxidant power. The present study revealed that NaF administration caused histological alterations in the cardiac muscle and increased the accumulation of intracellular reactive oxygen species, the expression of inducible nitric oxide synthases and proliferating cell nuclear antigen as well as collagen deposition in cardiac tissue. As supported by colorimetric analysis, an elevation in malondialdehyde level and a decrease in both superoxide dismutase (SOD) and thioredoxin-1 oxidoreductase (TrX) levels were seen, whereas molecular analysis revealed a decrease in Keap1 and an increase in Nrf2 and HO-1 gene expression. Pretreatment with vitamin C and PRP prior to NaF administration significantly improved the altered parameters and enhanced the cellular antioxidant capability of myocardium resulting in protection of cardiac muscle from NaF-induced cytotoxicity and apoptotic cell death. The cyto-protective activity of PRP was found to be comparable to that of the known antioxidant, vitamin C.

Genotoxicity of fluoride subacute exposure in rats and selenium intervention

The aims of this study were to: (i) examine the toxic effects of sodium fluoride (NaF) in blood, liver, spleen, and brain cells of Wistar rats after the subacute exposure; (ii) explore the potential protective properties of selenium (Se) against fluoride toxicity after the simultaneous administration. Twenty male Wistar rats, eight weeks old, weighing approximately 140–190 g, were divided into four experimental groups (n = 5) as follows: I control-tap water; II NaF 150 ppm; III NaF 150 ppm and Se 1.5 mg/L; IV Se 1.5 mg/L, and had available water with solutions ad libitum for 28 days. DNA damage detected by comet assay was confirmed in the liver, spleen, and brain cells, but not in blood. Selenium supplementation together with NaF decreased DNA damage in liver and spleen cells. According to the histological findings, no changes were observed in spleen and brain tissues after NaF administration. Unlike the observed Se protective effect on the DNA level, no significant reduction of liver tissue injury was observed after the NaF and Se treatment, resulting in mild inflammation. Data of this study suggest that DNA damage after NaF subacute exposure at moderately high concentration was reduced in liver and spleen cells due to Se supplementation, but a similar change was not seen in the brain.

BIOKINETIC AND DOSIMETRIC ASSESSMENT OF FLUORINE 18 IN HEALTHY VOLUNTEERS SUBJECTED TO 18F–NaF PET/CT BONE SCANS VIA COMPARTMENTAL/MATLAB MODELS AND IN-VIVO STUDY

Objective: This study quantified the time-dependent concentration of [Formula: see text]F–NaF in critical organs according to a simplified compartmental biokinetic model with clinical verification. Methods: The eleven volunteers were given [Formula: see text][Formula: see text]MBq [Formula: see text]F–NaF administration, then scanned (with 15[Formula: see text]min-collection, every 20[Formula: see text]min, for 200 consecutive min) with a Philips Gemini GXL PET/CT. The empirical data were collected and normalized as the input dataset for MATLAB program. A six-compartmental model was created as a set of time-dependent differential equations and analyzed by the MATLAB to optimize the correlation between the in vivo data and calculated results. The six compartments were: body fluid, bone, kidney, liver, remainder and excretion, while kidney and liver compartments were conventionally split into two subunits with different half-lives to fit properly the empirical data. Results: The average biological half-lives of body fluid, bone, kidney-1, kidney-2, liver-1, liver-2 and the remainder (rest of body) were assessed as [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text][Formula: see text]min, respectively. A dimensionless AT index of disagreement between the empirical data and MATLAB optimal solutions was proposed of validating the applied acquisition system and analytical method feasibility. The body fluid and bone AT values did not exceed 20%. The proposed refined equation yielded the internal dose from both gamma- and beta-rays ([Formula: see text] cSv as [Formula: see text] cSv/MBq), which exhibited good correlation with literature (0.00168–0.00270 cSv/MBq). Conclusion: The proposed MATLAB-based fitting of in-vivo data with the theoretical results was instrumental for assessing the radiation dose received by the PET/CT bone scan participants.

Nano-encapsulation of Dietary Phytoconstituent Capsaicin on Emulsome: Evaluation of Anticancer Activity Through the Measurement of Liver Oxidative Stress in Rats.

Excessive reactive species derived from oxygen and nitrogen leads to oxidative damage to tissue and organs. Capsaicin (CAP), a pungent component found in red pepper can prevent oxidative stress. The aim of the present work was to evaluate the protective effects of CAP loaded nano-emulsomes (EML) against the oxidative stress of rat livers induced through sodium fluoride (NaF). EML was prepared by thin film hydration method that is development of thin lipid film followed by hydration and sonication. EML was characterized by Fourier transform infrared (FT-IR) spectroscopy and X-ray diffraction (XRD) techniques. EML was evaluated for drug entrapment, in vitro drug release, and in vivo study. In vitro drug release study of optimized formulation showed that 50% of CAP was released within 50.21 min while 85% CAP was released in 227.4 min. Single oral dose of free CAP and CAP loaded EML were given to rats 2 hour after NaF administration. Membrane of hepatic cells was damaged by NaF and it was judged by the estimation of lipid peroxidation, reactive oxygen species (ROS), and catalase activity. The administration of CAP loaded EML 2 hr after NAF consumption showed significant decrease in ROS level compared to free CAP. EML containing CAP was more effective in comparison to free CAP in controlling the lipid peroxidation that is thiobarbituric acid substance augmentation in liver by the treatment of NaF. The administration of CAP loaded EML showed significant increase in catalase activity compared to free CAP administration. The results clearly demonstrated that CAP loaded EML may be accepted as an effective therapeutic formulation in preventing oxidative damage.

Sodium Fluoride Induces Hepato-Renal Oxidative Stress and Pathophysiological Changes in Experimental Animals

The liver is a primary site for xenobiotics detoxification, and its metabolism is readily altered by toxicity. The kidney is a common target for toxic xenobiotics due to its capacity to extract and concentrate toxic substances by highly specialized cells. So, they are the target organs of sodium fluoride toxicity. The aim of this review is to highlight on hepatorenal oxidative stress and pathophysiological changes induced by treatment of experimental animals with sodium fluoride. Our review shows fluoride toxicosis caused an elevation in the serum activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, acid phosphatase, and the level of total bilirubin, and reduction in the serum levels of total protein, albumin, and globulins, and serious histopathological changes in the hepaic tissues. Also, NaF administration caused increases in serum urea, creatinine, uric acid, sodium ions, and chloride ions levels and serious histopathological changes in the kidney tissues. Treatment of experimental animals with NaF induced oxidative stress in hepatic and renal tissues. It can be concluded that administration of sodium fluoride to experimental animals induced oxidative stress, serious hepatorenal histopathological changes, and disturbance in liver and kidney functions. So, human should be advised to decrease exposure to sodium fluoride to decrease the harmful effects of NaF on liver and kidney.

The Inhibition of Relapse of Orthodontic Tooth Movement by NaF Administration in Expressions of TGF-β1, Runx2, Alkaline Phosphatase and Microscopic Appearance of Woven Bone

The prevalence of post-treatment relapse in orthodontics in the community is high enough; therefore, relapses in orthodontic treatment must be prevented well. The aim of this study is to experimentally test the inhibition of relapse of orthodontics tooth movement in NaF of expression TGF-β1, Runx2, alkaline phosphatase (ALP) and microscopic of woven bone. The research method used was experimental laboratory research involving 30 rats, which were divided into three groups. Group A: rats were not given orthodontic tooth movement and without NaF. Group B: rats were given orthodontic tooth movement and without 11.5 ppm by topical application. Group C: rats were given orthodontic tooth movement and 11.75 ppm by topical application. Orthodontic tooth movement was conducted by applying ligature wires of 0.02 mm in diameter on the molar-1 (M-1) of left permanent maxilla and left insisivus of maxilla. Immunohistochemical examination was conducted to calculate the number of osteoblast to determine TGF β1, Runx2, ALP and haematoxylin to determine woven bone on day 7 and day 14. Results: It was shown that administrations of Natrium Fluoride topical application proved effective to increase the expression of TGF-β1, Runx2, ALP and to increase woven bone in the tension area greater than administration without natrium fluoride topical application (p < 0.05), except the expression of ALP on day 7 and day 14 which was significant. The results of the study show that NaF significantly increases the expressions of TGF-β1, Runx2, ALP and woven bone. The expression of the variables enhanced on day 7 compared on that on day 14, except ALP. Thus, it can be said that the acceleration of woven bone occurs on day 7.

Pathology of acute oral toxicity of sodium fluoride in Wistar rats

Toxicopathological effects of sodium fluoride (NaF) with acute toxic dose were studied in female Wistar rats. The acute toxic dose of NaF was determined by approximate lethal dose (ALD) method. The ALD for NaF was found to be 253.125 mg/kg body weight, orally in female Wistar rats. The rat showed signs of depression, prostration, piloerection, scant droppings, profuse salivation, initial colourless lacrimation followed by chromodacryorrhoea, dyspnoea, passage of dark reddish -black pasty faeces, gasping, cyanotic paws, hunched posture, soiled perineum and loss of reflexes. The rat died after 8 hours of oral NaF administration. The pathomorphological changes observed at necropsy were those of generalized congestion in vital organs i.e., liver, heart, kidneys, spleen and brain along with frothy catarrhal gastritis. Apart from haemorrhages and congestion in liver, lungs, kidneys and heart, the histopathological lesions represented degenerative and necrotic changes and dilated sinusoids in liver, degeneration and necrosis of tubular epithelium and glomeruli in kidneys, severe degenerative and necrotic changes in cardiac muscles, severe lymphocytolysis in the Malpighian corpuscles in spleen, thickening of interalveolar septa in lungs and mild degenerative and necrotic changes in neurons of brain.

In Vivo Protective Effects of Gallic Acid Isolated from Peltiphyllum Peltatum Against Sodium Fluoride-Induced Oxidative Stress in Rat Erythrocytes

Gallic acid has been identified as an antioxidant component of the edible and medicinal plant Peltiphyllum peltatum. The present study examined its potential protective role against sodium fluoride (NaF)-induced oxidative stress in rat erythrocytes. Oxidative stress was induced by NaF administration through drinking water (1030.675 mg m(-3) for one week). Gallic acid at 10 mg kg(-1) and 20 mg kg(-1) and vitamin C for positive controls (10 mg kg(-1)) were administered daily intraperitoneally for one week prior to NaF administration. Thiobarbituric acid reactive substances, antioxidant enzyme activities (superoxide dismutase and catalase), and the level of reduced glutathione were evaluated in rat erythrocytes. Lipid peroxidation in NaF-exposed rats significantly increased (by 88.8%) when compared to the control group (p<0.05). Pre-treatment with gallic acid suppressed lipid peroxidation in erythrocytes in a dose-dependent manner. Catalase and superoxide dismutase enzyme activities and glutathione levels were reduced by NaF intoxication by 54.4%, 63.69%, and 42% (p<0.001; vs. untreated control group), respectively. Pre-treatment with gallic acid or vitamin C significantly attenuated the deleterious effects. Gallic acid isolated from Peltiphyllum peltatum and vitamin C mitigated the NaF-induced oxidative stress in rat erythrocytes.

Protective effect of quercetin against sodium fluoride induced oxidative stress in rat's heart

The antioxidative and cardioprotective properties of quercetin were investigated against sodium fluoride (NaF) induced oxidative stress in rat hearts. Experimental rats were divided into five groups. The first group served as the untreated (normal) control. The second group received NaF at a dose of 600 ppm through drinking water for 1 week, and served as the toxin control. The third and fourth groups were exposed to quercetin (at the dose of 10 and 20 mg kg(-1) intraperitoneally (i.p.) for 1 week) prior to NaF intoxication, and the fifth group was treated with vitamin C at a dose of 10 mg kg(-1) i.p., for 1 week prior to NaF intoxication and served as the positive control in the study. The activities of various antioxidant enzymes, superoxide dismutase and catalase, level of reduced glutathione and lipid peroxidation end product were determined in the cardiac tissues of all the experimental animals. NaF intoxication significantly altered all the indices related to the pro-oxidant-antioxidant status of the heart; treatment with the active constituents prior to NaF administration, however, prevented these alterations. The combined results suggest that quercetin protects rat hearts from NaF-induced oxidative stress, probably via its antioxidant properties.

Effect of Sodium Fluoride Administration to Rats on Bone Phosphorous Content and Phosphatemia

Fluoride (F) has a known mitogenic effect on bone cells. The daily administration of 40 micromol NaF per 100 g of body weight (bw) increases bone mass in rats. Nevertheless, the quality and composition of bone formed under F stimulus is still matter of study. The objective of this work was to investigate the effect of sodium fluoride (NaF, CAS 7681-49-4) administration on phosphate metabolism and its impact on bone. Experiments were carried out in female fasted 50-day-old rats. Unless otherwise stated, NaF dose was 40 micromol NaF/day . 100 g bw, administered by gastric tube. Four groups of 4 rats each were given the following daily NaF doses: Group A: 0, B: 20, C: 40 and D: 60 micromol NaF/day x 100 g bw. After 30 days rats were killed saving their femora and plasma. Bone phosphorous contents (BPC) and phosphatemia (mg/dl) were measured. BPC decreased significantly as a function of NaF dose. A: 93.3+/-14.1; B: 78.7+/-15.5; C: 61.1+/-14.7**; D: 59.6+/-8.6 **mg P/g dry bone (** significant difference to group A, p < 0.01). Phosphatemia (mg/dl) increased significantly with a peak at 90 min after NaF dose (basal: 5.34+/-0.06; 90 min: 8.15 +/-0.43, p < 0.001). Phosphaturia (microg/min) increased though differences were not significant (basal: 46.7+/-42.8; 4 h: 1275 +/-757, p > 0.05). In thyroparathyroidectomized rats, plasma phosphate increased continuously for at least 240 min. Renal plasmatic flow, glomerular filtration rate and renal blood flow were not affected by NaF treatment. In isolated perfused rat kidneys, urinary phosphate excretion remained unaffected after NaF administration. Phosphate concentration was measured in the plasma and erythrocytes of rats after one dose of NaF (n = 8). Phosphate content of erythrocyte was not affected by NaF, in spite of the concurrent increase in phosphatemia. It is concluded that the treatment with NaF causes a transitory increase in plasma phosphate levels. Neither renal hemodynamic factors nor the inhibitory effect on parathormone actions appear to be the causes of hyperphosphatemia. Efflux of phosphate from cells might not be the cause of the increase in phosphatemia. The loss of phosphorous from bone appears as the most probable determinant of hyperphosphatemia after fluoride administration.

Efficacy of lycopene against fluoride toxicity in rats

Context: Oxidative damage to cellular components such as lipids and cell membranes by free radicals and reactive oxygen species (ROS) is thought to be associated with the development of degenerative diseases. Fluoride intoxication is associated with oxidative stress and altered anti-oxidant defense mechanism. Lycopene is a lipid-soluble powerful anti-oxidant that scavenges free radicals and ROS.Objective: This study was extended to investigate lycopene anti-oxidant efficacy in different organs of fluoride-intoxicated rats.Methods: Twenty-four adult rats were randomly divided into four groups of six animals each. Rats in group I received daily doses of vehicle. Group II rats were given lycopene (10 mg/kg body weight/day), by tubes, dissolved in 0.5 ml of corn oil for 5 weeks. Group III rats were given sodium fluoride (NaF) (10.3 mg/kg body weight/day), by tubes, for 5 weeks. In group IV rats, lycopene was administered 1 h later and NaF was administered for 5 weeks.Results: NaF administration induced oxidative stress as evidenced by elevated levels of lipid peroxidation (51.3, 65.9 and 67.6%) measured as malondialdehyde and total nitrate/nitrite (61.0, 59.7 and 68.9%) in red blood cells, heart and brain tissues. Moreover, significantly decreased reduced glutathione level, total anti-oxidant capacity and superoxide dismutase activity were observed in the examined tissues. The induced oxidative stress and the alterations in anti-oxidant system were normalized by the oral administration of lycopene treatment.Conclusion: Lycopene administration could minimize the toxic effects of fluoride indicating its free-radical scavenging and powerful anti-oxidant activities.

Evaluation of vitamin E and calcium effects on fluoride toxicity-induced fertility impairment

Chronic fluoride (Fl) toxicity is a serious public health problem globally where drinking water contains more than 1 ppm of Fl. Sodium fluoride (NaF) produced male reproductive system toxicity. The aim of the present study was to evaluate the amelioration of Fl toxicity-induced fertility impairment by vitamin E and calcium during the withdrawal period. The study was carried out on 70 adult male albino rats divided into five main groups: group I control; subdivided into group Ia (maintained on standard diet and water ad libitum for 60 days) and group Ib (maintained on standard diet and water ad libitum for 120 days), group II was administered NaF and subdivided into group IIa (administered NaF for 60 day and sacrificed) and group IIb (administered NaF for 60 day then maintained on standard diet and water ad libitum for a further 60 days), and treated groups III, IV, and V were administered NaF. Rats were maintained during withdrawal from NaF, on vitamin E (10 mg kg−1 day−1 for 60 days), calcium (50 mg kg−1 day−1 orally for 60 days), and both vitamin E and calcium, respectively. The duration of NaF administration was 60 days at a dose 20 mg kg−1 day−1 for all treated groups. The following parameters were determined: body and organ weights, sperm motility, sperm morphology, sperm viability, fertility test, and hormone assays: testosterone, in vitro testosterone production, luteinizing hormone, and follicular stimulating hormone. The combined administration of vitamin E and calcium during withdrawal from NaF showed significant improvement from chronic FL-induced toxicity on male reproductive organs.

Terminalia arjunaProtects Mouse Hearts Against Sodium Fluoride-Induced Oxidative Stress

Fluoride is a ubiquitous environmental pollutant. In the current study we have investigated the antioxidative properties of an ethanol extract of the bark of Terminalia arjuna (T. arjuna ethanol extract [TAEE]) against sodium fluoride (NaF)-induced oxidative stress in murine heart. Experimental mice were divided into four groups. The first group served as the normal control. The second group received NaF at a dose of 600 ppm through drinking water for 1 week and served as the toxin control. The third group was exposed to TAEE (at a dose of 50 mg/kg of body weight for 1 week) prior to NaF intoxication, and the last group was treated with vitamin C at a dose of 100 mg/kg body weight for 1 week prior to NaF intoxication and served as the positive control in the study. The activities of various antioxidant enzymes (superoxide dismutase, catalase, and glutathione S-transferase), levels of cellular metabolites, reduced glutathione, and oxidized glutathione, levels of lipid peroxidation end products, and protein carbonyl contents were determined in the cardiac tissues of all the experimental animals. NaF intoxication significantly altered all the indices related to the prooxidant-antioxidant status of the heart; treatment with the active constituents prior to NaF administration, however, prevented these alterations. In addition, the ferric reducing/antioxidant power assay revealed that TAEE enhanced the cardiac intracellular antioxidant activity. Histological studies also demonstrated a cardioprotective action of TAEE. The combined results suggest that TAEE protects murine hearts from NaF-induced oxidative stress, probably via its antioxidant properties.

Cytoprotective effect of arjunolic acid in response to sodium fluoride mediated oxidative stress and cell death via necrotic pathway

The present study was conducted to investigate the role of arjunolic acid (AA) against sodium fluoride (NaF)-induced cytotoxicity and necrotic cell death in murine hepatocytes. Dose-dependent studies suggest that incubation of hepatocytes with NaF (100mM) for 1h significantly decreased the cell viability as well as intracellular antioxidant power. Besides, NaF administration increased the activities of the membrane leakage enzymes and accumulation of intracellular reactive oxygen species; decreased the activities of the antioxidant enzymes, the glutathione (GSH) and total thiol contents; and elevated the level of oxidised glutathione (GSSG), lipid peroxidation end products as well as protein carbonyl content. In addition to the oxidative impairments, fluoride exposure caused hepatic cell death mainly via the necrotic pathway as supported by the flowcytometric and DNA fragmentation analyses. Incubation with AA (100 microg/ml) both prior to and in combination with NaF almost normalized the altered activities of antioxidant indexes. AA treatment enhanced the cellular antioxidant capability and protected hepatocytes against NaF-induced cytotoxicity and necrotic death. The cytoprotective activity of AA was found to be comparable to that of a known antioxidant, vitamin C. Combining, data suggest that AA plays a protective role against NaF-induced cellular damage and prevents hepatocytes from necrotic death.

HIV Tat Protein Increases Blood‐Brain Barrier Permeability: In Vitro and In Vivo Evidence

Tat protein is synthesized and released by HIV infected cells into the extracellular space. The current study is based on the hypothesis that circulatory Tat can increase permeability of the blood‐brain barrier (BBB). Carotid surgeries were performed on C57BL/6 mice under anesthesia. The common carotid artery, external carotid artery (ECA), and internal carotid artery (ICA) were isolated. The ECA was ligated with 6–0 silk suture distal from the ICA and cut distal from ligated point. A catheter was introduced into this incision and advanced into the ICA. Tat and control substances were injected into the ICA and allowed to circulate for up to 24 h. As the marker of the BBB permeability, mice received sodium fluorescence (Na‐F) injection through the same catheter. Five minutes following Na‐F administration, the brains were perfused and harvested. The permeability index was assayed as Na‐F brain/plasma content. Furthermore, expression of tight junction proteins was evaluated following Tat exposure in the brain tissues and cultured brain microvascular endothelial cells. Tat protein markedly increased the BBB permeability and decreased tight junction protein expression. These results provide additional evidence that Tat can play an important role in HIV‐1 trafficking into the brain, the event that precedes the development of HIV‐1‐associated encephalopathy. Supported by MH63022, MH072567, and NS39254.

A 43 kD Protein Isolated from the Herb Cajanus indicus L Attenuates Sodium Fluoride-induced Hepatic and Renal Disorders in Vivo

The herb, Cajanus indicus L, is well known for its hepatoprotective action. A 43 kD protein has been isolated, purified and partially sequenced from the leaves of this herb. A number of in vivo and in vitro studies carried out in our laboratory suggest that this protein might be a major component responsible for the hepatoprotective action of the herb. Our successive studies have been designed to evaluate the potential efficacy of this protein in protecting the hepatic as well as renal tissues from the sodium fluoride (NaF) induced oxidative stress. The experimental groups of mice were exposed to NaF at a dose of 600 ppm through drinking water for one week. This exposure significantly altered the activities of the antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione reductase (GR) and the cellular metabolites such as reduced glutathione (GSH), oxidized glutathione (GSSG), total thiols, lipid peroxidation end products in liver and kidney compared to the normal mice. Intraperitoneal administration of the protein at a dose of 2 mg/kg body weight for seven days followed by NaF treatment (600 ppm for next seven days) normalized the activities of the hepato-renal antioxidant enzymes, the level of cellular metabolites and lipid peroxidation end products. Post treatment with the protein for four days showed that it could help recovering the damages after NaF administration. Time-course study suggests that the protein could stimulate the recovery of both the organs faster than natural process. Effects of a known antioxidant, vitamin E, and a non-relevant protein, bovine serum albumin (BSA) have been included in the study to validate the experimental data. Combining all, result suggests that NaF could induce severe oxidative stress both in the liver and kidney tissues in mice and the protein possessed the ability to attenuate that hepato-renal toxic effect of NaF probably via its antioxidant activity.

Effect of Long-term Fluoride Exposure on Lipid Peroxidation and Histology of Testes in First- and Second-generation Rats

This experiment was designed to investigate the histological and lipid peroxidation effects of chronic fluorosis on testes tissues of first- and second-generation rats. Sixteen virgin female Wistar rats were mated with eight males (2:1) for approximately 12 h to obtain first-generation rats. Pregnant rats were divided into two groups: controls and fluoride-given group, each of which containing five rats. Pregnant rats in the fluoride-given group were exposed to a total dose of 30 mg/l sodium fluoride (NaF) in commercial drinking water containing 0.07 mg/l of NaF throughout the gestation and lactation periods. After the lactation period, the young animals (first generation, F1) were exposed to the same dose of NaF in drinking water for 4 months. At the end of the 4 months of experimental period, nine randomly chosen male rats (F1) were killed and testes tissues were taken for histopathological and biochemical analysis. The remaining eight female rats were mated with four males (2:1) for approximately 12 h to obtain second-generation rats. Six female were identified as pregnant and treated with similarly throughout the gestation and the lactation periods. After the lactation period, the young male animals (second generation, F2) were also treated in the same way for 4 months. At the end of the 4 months of experimental period, nine randomly chosen male rats (F2) were killed and testes tissues were collected for histopathological and biochemical analysis. The rats in the control group were applied the same procedure without NaF administration. In biochemical analysis of the fluoride given F1 and F2 rats, it has been found that plasma fluoride levels and testes thiobarbituric acid reactive substance levels were significantly increased when compared with the control group. In F1 and F2 rats, similar histopathological changes were observed. In both groups, spermatogenesis was severely reduced. Spermatogonia and primary spermatocytes were normal, however, there was a widespread degeneration in other spermatogenic cell lines of the seminiferous epithelium. The histological structures of the Sertoli and interstitial Leydig cells were normally observed. It is concluded that chronic fluorosis exposure leads to a remarkable destruction in testes tissues of F1 and F2 rats via lipid peroxidation.

Study of strontium and boron as antidotes to fluoride toxicity

The recovery from fluoride toxicity of white mice by strontium (Sr) and boron (B) was investigated. With the 2 mg NaF/kg body weight B.W./d treatment for 6 months, the body weights and the fluoride levels in livers of white mice had no significant changes in comparison with the control. However, the fluoride contents in bones sharply increased (p <0.01) after 1.5 months treatment. No significant variation in alkaline phosphatase (ALP) activity in serum was observed after 1.5 and 3.0 months NaF treatment, whereas, with NaF administration for 4.5 and 6.0 months, the ALP activities increased markedly (p <0.01). The ALP activity in kidneys was significantly higher than the control (p <0.01) after the white mice had maintained on water containing NaF for 1.5 months. When 2mg NaF/kg B.W./d was administered with 0.8 mg B/kg B.W./d and 1 mg Sr/kg B.W./d concurrently, fluoride levels in bones and ALP activities in serum and kidney was reduced compared with individual treatment of fluoride, which suggested that Sr and B could antagonize fluoride toxicity. The extent of recovery was somewhat more pronounced by B treatment than by Sr administration.

Cytogenetic studies of sodium fluoride in mice.

The cytogenetic effects of sodium fluoride (NaF) were measured in mice following administration in the drinking water for 6 weeks. Bone fluoride levels were determined and showed a dose-related incorporation of fluoride. Micronuclei were measured in peripheral blood erythrocytes following 1 and 6 weeks of NaF administration. Bone marrow cell preparations were examined for the presence of chromosome aberrations following 6 weeks of treatment; metaphase and anaphase cells were examined. Anaphase cells were scored in three independent laboratories, two of which also scored metaphase cells from the same slides. No increases in micronuclei were seen in peripheral erythrocytes at either time point, and no increases in chromosome aberrations were seen in bone marrow cells when metaphase or anaphase cells were examined. A concurrent positive control, cyclophosphamide, produced significant increases in peripheral blood cell micronuclei and in chromosome aberrations in bone marrow cells in metaphase. No increases in aberrations were seen in the same cyclophosphamide-treated mice when anaphase cells were examined.

Fluoride-induced bone changes in lambs during and after exposure to sodium fluoride

The evolution of bone changes induced by fluoride after the end of exposure was investigated in lambs. Sodium fluoride (NaF) was given orally at a dose of 3.5 mg/kg per day to 14 animals for 120 days. A group of 7 control and 7 treated lambs was slaughtered at the end of NaF administration (T120) and another group 120 days after the end of NaF exposure (T240). At T120, the bone fluoride content (BFC) was very significantly increased in treated animals. The histomorphometric analysis confirmed that fluoride induces an increase in bone formation (the osteoid perimeter and area were 3-fold and 4.5-fold higher respectively in treated than in control animals). The number of osteoblasts was significantly augmented. Serum osteocalcin level was twice as high in treated animals compared with controls. The bone formation rate at the tissue level (BFR) doubled after treatment, but the apposition rate (Aj.AR) was half that in the control group. The mineralization lag time (Mlt) was 120 days in treated animals compared with 42 days in controls. At T240, BFC had decreased by 50% compared with the level at T120, but it was still significantly higher than in controls. The osteoid and osteoblastic parameters were 2 and 1.3 times higher than in control animals. BFR remained significantly increased in treated animals, but Aj.AR and Mlt were similar in control and treated animals. In conclusion, after 4 months of NaF exposure fluoride induced an increase in osteoblast natality and bone formation at the tissue level, associated with a toxic effect at the individual cell level.(ABSTRACT TRUNCATED AT 250 WORDS)