Desensitizing Agent Previously Applied During In-Office Bleaching: A Double-Blind Randomized Clinical Trial

Abstract Objective: To compare the clinical effect of two desensitizing agents used before the application of a bleaching gel based on 35% hydrogen peroxide (HP). Material and Methods: 30 patients were selected, and two desensitizing agents with different mechanisms of action were applied: Fluorine Neutral 2% (FN), which acts by blocking dentinal canaliculi while Potassium Nitrate 5% with 2% Sodium Fluoride (PN/SF) that acts in nerve transmission and blockade. Desensitizers were used before the application of 35% HP. For whitening, three clinical sessions were performed, with an interval of seven days, with three applications of the bleaching gel for 15 minutes, totaling 45 minutes/session. Tooth sensitivity (TS) was assessed with the numerical analog scale, and a spectrophotometer was used to obtain the color variation (ΔE). ΔE were submitted to ANOVA and Tukey test (p<0.05), and TS data were submitted to a two-way ANOVA analysis. Results: For sensitivity experience, the Tukey test indicated differences between PN/SF and the placebo I, but there was no statistically significant difference between FN and the placebo II. The TS was lower when the desensitizing gel was used during the bleaching procedure compared to after treatment, regardless of the desensitizing agents. Conclusion: PN/SF before in-office tooth bleaching can reduce TS intensity, and the use of desensitizing gel before bleaching did not affect the bleaching efficacy.

Effects of long-term fluoride exposure are associated with oxidative biochemistry impairment and global proteomic modulation, but not genotoxicity, in parotid glands of mice.

BACKGROUND: Fluoride has become widely used in dentistry because of its effectiveness in caries control. However, evidence indicates that excessive intake interferes with the metabolic processes of different tissues. Thus, this study aimed to investigate the effects of long-term exposure to F on the parotid salivary gland of mice, from the analysis of oxidative, proteomic and genotoxic parameters. MATERIALS AND METHODS: The animals received deionized water containing 0, 10 or 50 mg/L of F, as sodium fluoride, for 60 days. After, parotid glands were collected for analysis of oxidative biochemistry, global proteomic profile, genotoxicity assessment and histopathological analyses. RESULTS: The results revealed that exposure to fluoride interfered in the biochemical homeostasis of the parotid gland, with increased levels of thiobarbituric acid reactive species and reduced glutathione in the exposed groups; as well as promoted alteration of the glandular proteomic profile in these groups, especially in structural proteins and proteins related to oxidative stress. However, genotoxic assessment demonstrated that exposure to fluoride did not interfere with DNA integrity in these concentrations and durations of exposure. Also, it was not observed histopathological alterations in parotid gland. CONCLUSIONS: Thus, our results suggest that long-term exposure to fluoride promoted modulation of the proteomic and biochemical profile in the parotid glands, without inducing damage to the genetic component. These findings reinforce the importance of rationalizing the use of fluorides to maximize their preventative effects while minimizing the environmental risks.

The value of the hedgehog signal in osteoblasts in fluoride-induced bone-tissue injury.

OBJECTIVE: This study was designed to observe the expression of important hedgehog (Hh) signal factors in the bone tissue of rats with chronic fluorosis and cultured osteoblasts in order to investigate the role and significance of the Hh signal in fluoride-induced bone injury. METHODS: Healthy Sprague-Dawley (SD) rats were randomly divided into four groups: the control group, the fluorosis group (F Group), the fluoride + blocker group (F + Cycl group: rats were treated with fluoride + cyclopamine), and the fluoride + blocker control group (F + DMSO group). After 6 months of intervention, the urinary fluoride content of rats in each group was detected. The primary osteoblasts of rats were selected for cell experiment, and the experiment was carried out after the cells were passaged from the second to the fourth generation. RESULTS: The proliferation rate of primary rat osteoblasts presented time-affected and dose-affected relationships in a short time under treatment with a low dose of sodium fluoride (NaF), but the proliferation of osteoblasts was inhibited by long-term and high-dose NaF exposure. In the F group, the alkaline phosphatase (ALP) activity of osteoblasts increased gradually. The ALP activity was lower in the F + Cycl group than in the F group, and there was no significant difference between the F + DMSO group and F group. With the increase in fluoride exposure, the expression of Hh signal factors and osteogenic-related factor proteins increased gradually. The expressions of Indian hedgehog (Ihh), smoothened (Smo), Glioma-associated oncogene homolog (Gli) 2, and Runt-related transcription factor 2 (Runx2)in the F + Cycl group increased with the dose of fluoride but they were significantly inhibited compared with the F group. Compared with the control group, the content of urinary fluoride in the F group was significantly higher (P < 0.05), but there was no significant change in urinary fluoride content in the F + Cycl group and the F + DMSO group. Compared with the control group, the serum bone alkaline phosphatase (BALP) contents of rats in the other groups increased after 6 months' intake of fluoride water (P < 0.05). After drug blocking, the serum BALP content in the F + Cycl group was lower than that in the F + DMSO group (P < 0.05). The BALP content in the F + DMSO group was similar to that in the F group: it did not decrease. The mRNA expressions of Ihh, Smo, Gli2, and Runx2 in bone tissue of the F group were significantly higher than those in the control group (P < 0.05). After cyclopamine blocking, the expressions decreased (P < 0.05), but the differences between the F + DMSO group and F group were not statistically significant. CONCLUSION: Hh signal plays an important role in fluoride-induced bone injury. The effective inhibition of cyclopamine is expected to be a new target for the treatment of skeletal damage caused by fluorosis.

La exposición prenatal a fluoruro induce cambios en la porción coronal de la cripta ósea y altera la erupción dental en crías lactantes / Prenatal fluoride exposure induces changes in the coronal portion of bony crypt and alters dental eruption in suckling rats

La erupción dental es un proceso estrictamente regulado y programado espacial y temporalmente. El objetivo del trabajo fue estudiar el efecto de la exposición prenatal a fluoruro de sodio (NaF) sobre los eventos morfológicos y celulares que ocurren en el hueso supracoronal del primer molar de crías de rata durante la etapa preeruptiva. Se emplearon crías (n=6-8 por grupo) provenientes de madres que bebieron crónicamente agua con diferentes concentraciones de F- en forma de NaF durante la gestación y lactancia: control y NaF (50 mg/L). En cortes histológicos de la mandíbula de crías de 3 y 10 días se analizaron parámetros de histomorfometría estática en la zona supracoronal de la canastilla ósea a la altura del primer molar inferior: volumen óseo trabecular [BV/TV (%)], número de osteoclastos por milímetro (N.Oc/mm) y las variables indirectas: número de trabéculas [Tb.N (1/mm)], espesor [Tb.Th (µm)] y separación trabecular [Tb.Sp (µm)]. En crías de 15 días se midió el grado de erupción [TED (µm)] del primer molar inferior. Los resultados se analizaron con el test "t" de Student considerando diferencias significativas a p<0,05. El análisis histomorfométrico demostró un incremento en el BV/TV (%) del hueso supracoronal (p<0,01) asociado con disminución del N.Oc/mm (p<0,01) en crías de 3 y 10 días expuestas prenatalmente al F-. El grado de erupción dental fue menor en animales expuestos prenatalmente al F- en comparación con los controles (p<0,01). En conclusión, los resultados observados en la mandíbula de crías expuestas durante la etapa prenatal y posnatal temprana al F- sugieren un efecto disruptivo sobre la actividad resortiva necesaria para formación del canal eruptivo. (AU)

Tooth eruption is a tightly regulated and spatially and temporally programmed process. The aim of this study was to examine the effect of prenatal NaF exposure on the morphological and cellular events that occur in the supracoronal area of bony crypt of the first rat molar during the preeruptive stage. Offspring from two groups of rats were used (6-8 per group): Control and 50 mg/L NaF. The treatment was performed during pregnancy and lactation. Suckling pups were euthanized at 3-, 10- and 15-days-old by cervical dislocation. Mandibles were removed and histologically processed to obtain buccolingual sections stained with H&E. In sections of first mandibular molar of 3- and 10-days-old pups, the following static histomorphometric parameters were evaluated: trabecular bone volume [BV/TV (%)] and number of osteoclasts (N.Oc/mm). Also, indirect parameters were obtained: trabecular number [Tb.N (1/mm)], trabecular thickness [Tb.Th (µm)], and trabecular separation [Tb.Sp (µm)]. The degree of tooth eruption [TED (µm)] was determined. Results are expressed as mean ± SE and analyzed by Student t-test. Histomorphometric analysis showed an increase in the BV/TV (%) of the bone crypt of 3- and 10- days-old pups exposed to NaF (p <0.01); this increase was associated with a decrease in the N.Oc/mm (p <0.01). TED of mandibular first molar was lower in prenatal NaF exposed group than in control group (p<0.01). In conclusion, the increased BV/TV and the lower N.Oc observed in the bone crypt of 3- and 10- days-old pups from mothers treated with NaF suggested a disruptive effect triggered by F- on the formation events of the eruptive pathway in the offspring. (AU)

Probiotic Lactobacillus johnsonii BS15 Prevents Memory Dysfunction Induced by Chronic High-Fluorine Intake through Modulating Intestinal Environment and Improving Gut Development.

In recent years, the influence of chronic fluorosis on the brain has been widely reported. Our study aimed to demonstrate the potential mechanism underlying the impairment of memory function by excessive fluorine intake. We also evaluated whether improvement of intestinal microflora could be a potential therapy to prevent the negative influences from the perspective of gut-brain axis. Male ICR mice were randomly divided into three groups and administered with either phosphate buffered saline (PBS) (Control and F groups) or Lactobacillus johnsonii BS15 (FP group; daily amounts of 1 × 109 CFU/mL), a probiotic strain, by oral gavage throughout a 98-day experimental period. Sodium fluoride (100 mg/L) was added to the drinking water of the F and FP groups. Animals were sacrificed for sampling with or without water avoidance stress (WAS) at two phases of the experiment and behavioral tests including T-maze test and passive avoidance test were also performed. Based on the results of behavioral tests, probiotic reversed the fluorine-induced memory dysfunction. In addition, L. johnsonii BS15 also increased the antioxidant capacities (serum and hippocampal tissue) and hippocampal synaptic plasticity-related mRNA expression after excessive fluoride ingestion. Moreover, the increased colonization of L. johnsonii BS15 also protected the small intestines from the damages of growth performance, visceral indexes, intestinal development, digestive, and secretory functions by changing the structure of the microflora and then improving intestinal permeability and integrity. L. johnsonii BS15 also improved the ability of flourosis mice against psychological stress indicated by the changes in behavioral tasks, hippocampal antioxidant levels, and synaptic plasticity-related mRNA expressions. Lactobacillus johnsonii BS15 intake appears as a promising way to ameliorate fluorine-induced memory dysfunction, especially under psychological stress.

Sodium Fluoride and Fluoride Contaminated Ground Water Induced Altered Reproductive Performances in Male Rats.

Present study was undertaken to investigate the toxic effect of sodium fluoride (NaF)- and fluoride (F)-contaminated ground water on reproductive performances of male rats. Healthy adult male rats were categorised into three groups, first group of rats were served as control, whereas second group of rats were orally intubated with NaF (10 mg/kgbw/1 ml/rat) and third group of rats were allowed to drink F-contaminated ground water (5 mg/L) through drinking water bottles for 52 days. Exposure of NaF- and F-contaminated ground water caused significant decline in sperm motility, serum concentration of testosterone, and increase in sperm abnormality compared with controls. Further, significant histological alterations characterized with shrunken seminiferous tubules and degeneration of different stages of spermatogonial cells were observed in rats treated with NaF- and F-contaminated ground water. After the confirmation of toxic effect of F, these NaF- and F-contaminated ground water-treated male rats were allowed to mate with proven fertile untreated female rats to study the reproductive performances of male rats. There was a decline in parturition index, fertility index of male and female, gestation index and number of pups delivered in NaF-treated male rats compared with controls. However, gestation index and number of pups delivered were declined in F-contaminated ground water-treated male rats compared with controls. These results clearly indicate that F exposure affected the reproductive performances of male rats. The present study further revealed the fact that F-induced decline in testosterone levels, reduced sperm motility, and loss of spermatogonial cells affected the reproductive performances of male rats.

GSTO1 acts as a mediator in sodium fluoride-induced alterations of learning and memory related factors expressions in the hippocampus cell line.

The mechanism of GSTO1, as a high-risk factor for neurological damage, in sodium fluoride (NaF)-induced learning and memory impairment remained still unclear. Hence, in this study, we used the siRNA-GSTO1 HT22 model to explore the effect of NaF and siRNA-GSTO1 on the viability, and proliferation rate of HT22 cells, as well as the mRNA and protein expression levels of cyclic adenosine monophosphate (cAMP) response element binding protein (CREB), neural cell adhesion molecule (NCAM), stem cell factor (SCF) and brain-derived neurotrophic factor (BDNF). The results of MTT showed that 10-3, 10-4, and 10-5 moL/L sodium fluoride (NaF) exposure could significantly promote the proliferation of HT22 cells at 24 h, 36 h, and 48 h, respectively. In addition, our results showed that exposure to 10-3, 10-4, and 10-5 moL/l NaF increased GSTO1 mRNA and protein expression, but decreased CREB and BDNF expression levels in a dose and time-dependent manner. The mRNA and protein expressions of GSTO1, CREB and BDNF were significantly decreased in the siRNA-GSTO1 and NaF + siRNA-GSTO1 group (P < 0.05). We have shown that various NaF doses affected the learning and memory ability by down-regulation the expressions of CREB, BDNF, NCAM and SCF. In summary, we concluded that GSTO1 plays a mediator role in NaF-induced neurological damage.

The Effect of Silver Diamine Fluoride in Preventing Caries in the Primary Dentition: A Systematic Review and Meta-Analysis.

OBJECTIVES: To investigate whether silver diamine fluoride (SDF) is effective in preventing new caries lesions in primary teeth when compared to placebo or active treatments. METHODS: Systematic review (CRD42016036963) of controlled clinical trials. Searches were performed in 9 electronic databases, 5 registers of ongoing trials, and reference lists of identified review articles. Two researchers carried out data extraction and quality appraisal independently. The primary outcome was the difference in caries increment (decayed, missing, and filled surfaces or teeth - dmfs or dmft) between SDF and control groups. These differences were pooled as weighted mean differences (WMD) and prevented fractions (PF). RESULTS: Searches yielded 2,366 unique records; 6 reports of 4 trials that randomized 1,118 and analyzed 915 participants were included. Two trials compared SDF to no treatment, 1 compared SDF to placebo and sodium fluoride varnish (FV), and 1 compared SDF to high-viscosity glass ionomer cement (GIC). All studies had at least 1 domain with unclear or high risk of bias. After 24 months of follow-up, in comparison to placebo, no treatment, and FV, SDF applications significantly reduced the development of new dentin caries lesions (placebo or no treatment: WMD = -1.15, PF = 77.5%; FV: WMD = -0.43, PF = 54.0%). GIC was more effective than SDF after 12 months of follow-up but the difference between them was not statistically significant (WMD, dmft: 0.34, PF: -6.09%). CONCLUSION: When applied to caries lesions in primary teeth, SDF compared to no treatment, placebo or FV appears to effectively prevent dental caries in the entire dentition. However, trials specifically designed to assess this outcome are needed.

Surface damage of dental implant systems and ions release after exposure to fluoride and hydrogen peroxide.

OBJECTIVE: The aim of this study was to evaluate surface changes on dental implant systems and ions release after immersion in fluoride and hydrogen peroxide. METHODS: Ten implant-abutment assemblies were embedded in acrylic resin and cross-sectioned along the implant vertical axis. Samples were wet ground and polished. Delimited areas of groups of samples were immersed in 1.23% sodium fluoride gel (F) or in 35% hydrogen peroxide (HP) for 16 min. Gels (n = 3) were collected from the implant surfaces and analyzed by inductively coupled plasma mass spectrometry (ICP-MS), to detect the concentration of metallic ions released from the implant systems. Selected areas of the abutment and implant (n = 15) were analyzed by atomic force microscopy (AFM) and scanning electron microscopy (SEM). RESULTS: SEM images revealed surface topographic changes on implant-abutment joints after immersion in fluoride. Implants showed excessive oxidation within loss of material, while abutment surfaces revealed intergranular corrosion after immersion in fluoride. ICP-MS results revealed a high concentration of Ti, Al, V ions in fluoride after contact with the implant systems. Localized corrosion of implant systems could not be detected by SEM after immersion in hydrogen peroxide although the profilometry showed increase in roughness. ICP-MS showed the release of metallic ions in hydrogen peroxide medium after contact with dental implants. CONCLUSION: Therapeutical substances such as fluorides and hydrogen peroxide can promote the degradation of titanium-based dental implant and abutments leading to the release of toxic ions.

Efeito anti-erosivo de soluções contendo diferentes polímeros / Anti-erosive effect of solutions containing different polymers

O desgaste erosivo tem sido reconhecido como uma condição frequente nos últimos anos, principalmente devido a mudanças nos hábitos alimentares e comportamentais das populações em geral. Considerando a natureza irreversível desta condição, o diagnóstico precoce e a adoção de medidas preventivas são muito importantes. Dentre elas, a adição de polímeros a produtos de higiene bucal associados ou não a fluoretos apresenta-se como uma alternativa promissora, já que alguns polímeros apresentam compatibilidade com as estruturas dentais e capacidade de formação de um filme protetor. Este estudo foi subdivido em três artigos que visaram, através de diferentes abordagens, investigar o efeito anti- erosivo de polímeros formadores de filme, bem como o efeito da associação destes com fluoretos. O primeiro artigo consistiu em uma revisão da literatura sobre aspectos relacionados ao potencial de utilização dos polímeros para a prevenção da erosão dental. O segundo artigo consistiu em um estudo de varredura para verificar a capacidade de redução da dissolução da hidroxiapatita promovida por soluções contendo quatro polímeros (polioxirano, hidroxipropilmetilcelulose, pectina e um copolímero do polimetacrilato) associadas ou não com fluoreto de sódio -F (225 ppm F- ) e fluoreto de sódio + cloreto de estanho (800 ppm Sn2+) - FS. A mensuração do potencial zeta da hidroxiapatita dispersa tratada com as soluções experimentais foi realizada a fim de complementar a análise. O terceiro artigo consistiu em um estudo de ciclagem erosiva/reendurecedora na presença de película adquirida que se propôs a investigar o potencial de remineralização, potencial de proteção, a perda superficial e a tensão superficial do esmalte após o tratamento com as soluções contendo o copolímero do polimetacrilato. Concluiu- se que a utilização de polímeros formadores de filme, associados ou não a fluoretos, constitui uma abordagem promissora para prevenção da erosão dental. Dentre os polímeros investigados, o copolímero do polimetacrilato é um promissor agente para ser adicionado à produtos de higiene bucal visando a prevenção dos desgastes erosivos(AU)

Erosive wear has been recognized as a frequent condition in recent years, mainly due to changes in the dietary and behavioral habits of the general population. Considering the irreversible nature of this condition, early diagnosis and the adoption of preventive measures are very important. Among them, the addition of polymers to oral care products associated or not with fluorides is a promising alternative, as some polymers have compatibility with dental structures and ability to form a protective film. This study was subdivided into three articles that aimed, through different approaches, to investigate the anti-erosive effect of film- forming polymers, as well as the effect of their association with fluorides. The first article consisted of a literature review about aspects related to the potential use of polymers to prevent dental erosion. The second article consisted of a scanning study to verify the ability to decrease the hydroxyapatite dissolution promoted by solutions containing four polymers (polyoxyrane, hydroxypropyl methylcellulose, pectin and a polymethacrylate copolymer) associated or not with sodium fluoride -F (225 ppm F- ) and sodium fluoride + tin chloride (800 ppm Sn2+ ) -FS. Measurement of the zeta potential of dispersed hydroxyapatite treated with experimental solutions was performed to complement the analysis. The third article consisted of an erosive/rehardening cycling study in the presence of acquired pellicle that aimed to investigate remineralization potential, protection potential, surface loss and surface tension of the enamel after treatment with solutions containing the polymethacrylate. It was concluded that the use of film- forming polymers, associated or not with fluorides, is a promising approach for the prevention of dental erosion. Among the polymers investigated, the polymethacrylate copolymer is a promising agent to be added to oral hygiene products to prevent erosive wear(AU)

Sodium Fluoride Arrests Renal G2/M Phase Cell-Cycle Progression by Activating ATM-Chk2-P53/Cdc25C Signaling Pathway in Mice.

BACKGROUND/AIMS: Excessive fluoride intake can induce cytotoxicity, DNA damage and cell-cycle changes in many tissues and organs, including the kidney. However, the underlying molecular mechanisms of fluoride-induced renal cell-cycle changes are not well understood at present. In this study, we used a mouse model to investigate how sodium fluoride (NaF) induces cell-cycle changes in renal cells. METHODS: Two hundred forty ICR mice were randomly assigned to four equal groups for intragastric administration of NaF (0, 12, 24 and 48 mg/kg body weight/day) for 42 days. Kidneys were taken to measure changes of the cell-cycle at 21 and 42 days of the experiment, using flow cytometry, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot methods. RESULTS: NaF, at more than 12 mg/kg body weight, induced G2/M phase cell-cycle arrest in the renal cells, which was supported by the finding of significantly increased percentages of renal cells in the G2/M phase. We found also that G2/M phase cell-cycle arrest was accompanied by up-regulation of p-ATM, p-Chk2, p-p53, p-Cdc25C, p-CDK1, p21, and Gadd45a protein expression levels; up-regulation of ATM, Chk2, p53, p21, and Gadd45a mRNA expression levels; down-regulation of CyclinB1, mdm2, PCNA protein expression levels; and down-regulation of CyclinB1, CDK1, Cdc25C, mdm2, and PCNA mRNA expression levels. CONCLUSION: In this mouse model, NaF, at more than 12 mg/ kg, induced G2/M phase cell-cycle arrest by activating the ATM-Chk2-p53/Cdc25C signaling pathway, which inhibits the proliferation of renal cells and development of the kidney. Activation of the ATM-Chk2-p53/Cdc25C signaling pathway is the mechanism of NaF-induced renal G2/M phase cell-cycle arrest in this model.

Chronic Exposure to Sodium Fluoride Triggers Oxidative Biochemistry Misbalance in Mice: Effects on Peripheral Blood Circulation.

The excessive fluoride (F) exposure is associated with damage to cellular processes of different tissue types, due to changes in enzymatic metabolism and breakdown of redox balance. However, few studies evaluate doses of F compatible with human consumption. Thus, this study evaluated the effects of chronic exposure to sodium fluoride (NaF) on peripheral blood of mice from the evaluation of biochemical parameters. The animals were divided into three groups (n = 10) and received three concentrations of NaF in the drinking water for 60 days: 0 mg/L F, 10 mg/L F, and 50 mg/L F. The blood was then collected for trolox equivalent antioxidant capacity (TEAC), thiobarbituric acid reactive substances (TBARS), concentrations of nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH). The results showed that doses of 10 mg/L F and 50 mg/L F were able to increase TBARS concentration and decrease NO levels and CAT activity in the blood, but there was no statistical difference for SOD levels. The 50 mg/L F group showed an increase in TEAC levels and a decrease in the GSH content when compared to the control group. In this way, oxidative changes in blood from chronic exposure to F, especially at the highest dose, indicate that F may be a toxic agent and, therefore, the long-term exposure to excessive doses should be avoided.

Possible protective effect of curcumin on the thyroid gland changes induced by sodium fluoride in albino rats: light and electron microscopic study.

OBJECTIVES: Thyroid gland regulates the body's metabolic rate and plays an exquisitely important role in the human health. Fluoride exposure can affect thyroid function. Curcumin is a potent antioxidant that works through several mechanisms. The aim of the present study was to demonstrate the hormonal, histological, and ultrastructural changes occurred in the thyroid gland induced by exposure to sodium fluoride (NaF) and study the possible protective effect of curcumin on the NaF-induced effects. METHODS: Thirty male albino rats were randomly divided into 3 equal groups (10 rats each): the control group, NaF group, and NaF+Curcumin (NaF+Cur) group. Thyroid-stimulating hormone (TSH), triiodothyronine (T3) and thyroxine (T4) levels were assayed and thyroid tissues processed for light and transmission electron microscopic study. RESULTS: In NaF group, serum T3 and T4 levels were significantly decreased whereas TSH level was significantly increased compared to the control group. Thyroid tissues showed flattening of the epithelial lining with several follicular cell degenerations, hyperplasia, decreased colloid, disrupted basement membrane, cytoplasmic vacuolations, degenerated mitochondria, widening of rough endoplasmic reticulum cisternae, and vascular congestion compared to the control group. In the NaF+Cur group, serum TSH levels were significantly decreased in comparison with NaF group and no significant difference in comparison with the control group. Thyroid sections appeared apparently normal compared to the control group and NaF group. CONCLUSIONS: Sodium fluoride affected both the function and structure of the thyroid gland while curcumin was protective against these toxic effects.

Fluoride-induced iron overload contributes to hepatic oxidative damage in mouse and the protective role of Grape seed proanthocyanidin extract.

Emerging evidence has demonstrated that iron overload plays an important role in oxidative stress in the liver. This study aimed to explore whether fluoride-induced hepatic oxidative stress is associated with iron overload and whether grape seed proanthocyanidin extract (GSPE) alleviates oxidative stress by reducing iron overload. Forty Kunming male mice were randomly divided into 4 groups and treated for 5 weeks with distilled water (control), sodium fluoride (NaF) (100 mg/L), GSPE (400 mg/kg bw), or NaF (100 mg/L) + GSPE (400 mg/kg bw). Mice exposed to NaF showed typical poisoning changes of morphology, increased aspartate aminotransferase and alanine aminotransferase activities in the liver. NaF treatment also increased MDA accumulation, decreased GSH-Px, SOD and T-AOC levels in liver, indicative of oxidative stress. Intriguingly, all these detrimental effects were alleviated by GSPE. Further study revealed that NaF induced disorders of iron metabolism, as manifested by elevated iron level with increased hepcidin but decreased ferroportin expression, which contributed to hepatic oxidative stress. Importantly, the iron dysregulation induced by NaF could be normalized by GSPE. Collectively, these data provide a novel insight into mechanisms underlying fluorosis and highlight the potential of GSPE as a naturally occurring prophylactic treatment for fluoride-induced hepatotoxicity associated with iron overload.

Identification of miR-200c-3p as a major regulator of SaoS2 cells activation induced by fluoride.

The skeletal lesion of fluoride has become a major concern in many countries due to its damage to bone and joints and even leading to disability. Skeletal fluorosis is characterized by disturbance of bone metabolism, aberrant proliferation and activation of osteoblasts is critical for the pathogenesis. However, the mechanism underlying the osteotoxicity of fluoride has not been clearly illustrated and there is still limited information on the role of miRNAs in skeletal fluorosis. In this study, we found that NaF promoted SaoS2 proliferation and activation by activating BMP4/Smad pathway. NaF increased expression of miR-200c-3p and miR-200c-3p inhibitor reduced activation of SaoS2 induced by NaF via targeting Noggin to repress BMP4/Smad. These findings suggested an important regulatory role of miR-200c-3p on BMP4/Smad pathway during skeletal fluorosis. MiR-200c-3p might be a novel therapeutic target for skeletal fluorosis.

Sodium fluoride does not affect the working memory and number of pyramidal cells in rat medial prefrontal cortex.

Fluoride is a chemical compound known to bring about fluorosis. It is thought to disrupt the central nervous system because of its ability to induce excitotoxicity and oxidative stress. Any damage of pyramidal cells in the prefrontal cortex would result in cognitive function and working memory regulation disorders. The present study aimed at investigating the effects of sodium fluoride (NaF) on the working memory and estimated total number of medial prefrontal cortex pyramidal cells of adult male rats. Thirty-two male Wistar rats were assigned into four groups, namely control and three treated groups receiving 5, 10 and 20 mg/kg BW, respectively, of oral NaF solution for 30 days. The working memory test was carried out using a Y-maze. The number of pyramidal cells in the medial prefrontal cortex was estimated using an unbiased stereological method. There was no significant difference among groups in the working memory and number of pyramidal neurons in the medial prefrontal cortex cells.

Taurine reverses sodium fluoride-mediated increase in inflammation, caspase-3 activity, and oxidative damage along the brain-pituitary-gonadal axis in male rats.

Excessive exposure to fluoride is associated with male reproductive dysfunction in humans and animals. Taurine (2-aminoethane sulfonic acid) is a free intracellular ß-amino acid with antioxidant, anti-inflammatory, and neuroprotective properties. However, the effect of taurine on fluoride-induced reproductive toxicity has not been reported. The present study investigated the influence of taurine on sodium fluoride (NaF)-induced functional changes along the brain-pituitary-gonadal axis in male rats. NaF was administered singly in drinking water at 15 mg·L-1 alone or orally co-administered by gavage with taurine at 100 and 200 mg·(kg body mass)-1 for 45 consecutive days. Results showed that taurine significantly prevented NaF-induced increase in oxidative stress indices as well as augmented antioxidant enzymes activities and glutathione level in the brain, testes, and epididymis of the treated rats. Moreover, taurine reversed NaF-induced elevation in inflammatory biomarkers and caspase-3 activity as well as histological damage in the brain, testes, and epididymis of the treated rats. The significant reversal of NaF-induced decreases in testosterone level and testicular activities of acid phosphatase, alkaline phosphatase, and lactate dehydrogenase by taurine was accompanied by enhancement of sperm functional characteristics in the treated rats. Taurine may be a possible chemopreventive candidate against reproductive dysfunction resulting from fluoride exposure.

Sodium fluoride causes oxidative stress and apoptosis in the mouse liver.

The current study was conducted to investigate the effect of sodium fluoride (NaF) on the oxidative stress and apoptosis as well as their relationship in the mouse liver by using methods of flow cytometry, quantitative real-time polymerase chain reaction (qRT-PCR), western blot, biochemistry and experimental pathology. 240 four-week-old ICR mice were randomly divided into 4 groups and exposed to different concentration of NaF (0 mg/kg, 12 mg/kg, 24 mg/kg and 48 mg/kg) for a period of 42 days. The results showed that NaF caused oxidative stress and apoptosis. NaF-caused oxidative stress was accompanied by increasing reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and decreasing mRNA expression levels and activities of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GSH-PX) and glutathione-s-transferase (GST). NaF induced apoptosis via tumor necrosis factor recpter-1 (TNF-R1) signaling pathway, which was characterized by significantly increasing mRNA and protein expression levels of TNF-R1, Fas associated death domain (FADD), TNFR-associated death domain (TRADD), cysteine aspartate specific protease-8 (caspase-8) and cysteine aspartate specific protease-3 (caspase-3) in dose- and time-dependent manner. Oxidative stress is involved in the process of apoptotic occurrence, and can be triggered by promoting ROS production and reducing antioxidant function. NaF-caused oxidative stress and apoptosis finally impaired hepatic function, which was strongly supported by the histopathological lesions and increased serum alanine amino transferase (ALT), aspartic acid transferase (AST), alkaline phosphatase (AKP) activities and TBIL contents.