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1.
Arch Oral Biol ; 111: 104638, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31901573

RESUMO

OBJECTIVE: The purpose of this study was to investigate the effects of Lemon essential oil (LEO) and Limonene (LIM) in the progress of early caries. DESIGN: LEO and LIM were selected as experimental medicine, while sodium fluoride (NaF) and deionized water (DW) were positive and blank controls, respectively. Bovine incisors were used to establish enamel and dentin early caries models by demineralization method in vitro. Then specimens were subjected to pH cycling. Calcium and phosphate release of demineralizing solution were measured by an automatic biochemical analyzer; Surface microhardness tester and energy dispersive X-ray spectrometer were used to detect the surface microhardness recovery and calcium- phosphate ratio on tooth surface; Degraded collagen matrix by collagenase was investigated by assaying hydroxyproline. RESULTS: Calcium release of dentin demineralizing solution of LEO group was lower than DW group's and higher than NaF group's. Both of LEO and LIM groups, the surface microhardness recovery were significantly lower than those of NaF group, which were similar to DW group. Dentin surface calcium- phosphate ratio of LEO and LIM groups were lower than those of NaF group and higher than those of DW group. Hydroxyproline concentration in the remineralizing solution of LEO and LIM groups were lower than DW groups' and higher than NaF groups'. CONCLUSIONS: LEO and LIM have influence on the progress of dentin early caries, which can stabilize its structure by inhibiting collagen degradation. Meanwhile, these medicines may provide a new drug choice for the prevention and treatment of early root caries.


Assuntos
Cariostáticos/farmacologia , Cárie Dentária , Esmalte Dentário/efeitos dos fármacos , Limoneno/farmacologia , Óleos Voláteis/farmacologia , Óleos Vegetais/farmacologia , Animais , Bovinos , Concentração de Íons de Hidrogênio , Fluoreto de Sódio/farmacologia , Desmineralização do Dente , Remineralização Dentária
2.
Arch Oral Biol ; 110: 104619, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31805483

RESUMO

OBJECTIVE: The aim of this study was to evaluate the morphological and chemical effect of in-office and at-home desensitising agents containing sodium fluoride (NaF) on eroded root dentine in vitro. METHODS: Fifty bovine dentine samples were pre-eroded and randomised into five groups (n = 10): G1 (Control) - milli-Q water; G2 - fluoride varnish containing NaF 22,500 ppm; G3 - desensitising cream containing NaF 9,000 ppm associated with 20% nanohydroxyapatite; G4 - toothpaste with NaF 5,000 ppm associated to tricalcium phosphate; G5 - toothpaste containing NaF 900 ppm and casein phosphopeptide-amorphous calcium phosphate fluoride (CPP-ACPF). The specimens were submitted to erosive challenge for three days. The analyses were performed using non-contact profilometry for volumetric (Sa) and linear roughness (Ra) followed by scanning electron microscopy (SEM) and Energy Dispersive X-ray Spectrometry (EDS). The data were analysed by Kruskal-Wallis and Wilcoxon tests (α = 0.05). RESULTS: There was a significant reduction of Ra and Sa for the eroded samples from the G2 and G5 (p < 0.05) after an erosive challenge. The dentine surface topography pattern showed partially or totally occluded dentinal tubules after treatments, except in the control group. The control, G4 and G3 groups showed a reduction in the dentine inorganic content percentage of Ca (Calcium) and P (Phosphorus) minerals. CONCLUSION: The fluoride varnish and CPP-ACPF toothpaste were able to prevent morphological changes and were the only materials that showed the Ca and P content increased after treatment. These materials may be promising alternatives in the clinical control of dentin erosion.


Assuntos
Dentina , Fluoreto de Sódio , Erosão Dentária , Raiz Dentária , Animais , Bovinos , Dentina/efeitos dos fármacos , Fluoretos , Fluoreto de Sódio/farmacologia , Erosão Dentária/tratamento farmacológico , Raiz Dentária/efeitos dos fármacos , Cremes Dentais
3.
Arch Oral Biol ; 106: 104482, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31325718

RESUMO

OBJECTIVE: The aim of the study was to determine demineralisation inhibition and remineralisation potential of poly-γ-glutamic acid with its possible mechanism of action on human dental enamel. METHODOLOGY: Three sodium-fluoride(NaF) concentration(0.01%w/v,0.1%w/v and 0.5%w/v respectively)and two poly-γ-glutamic acid(PGGA)concentration(1%w/v and 2%w/v respectively)were prepared in 0.1 M acetic acid(pH4.0)and deionized distilled water.For de/re-mineralisation study, tooth samples (18 teeth varnished, leaving a 2 mm2 window on the mid-buccal surfaces) were immersed in respective acidified NaF and PGGA solutions. The Ca2+ release/uptake was monitored with ISE over 72-hr with increasing pH every 24-h from 4.0 to 6.0.These teeth were later subjected to cross-sectional microhardness to determine integrated mineral recovery of enamel on increasing pH of respective acidified solution.In order to determine mechanism of PGGA,two concentrations of PGGA in deionized-water-solutions were used for tooth samples immersion followed by overnight drying then later subjected to Fourier Transform Infra-Red(FT-IR) analysis.The FT-IR analysis was also carried out on PGGA powder.For control,the experiment was repeated using hydroxyapatite(HAp)pellets.The density of PGGA solutions(1%and2%)was also measured to determine their dynamic viscosities. RESULTS: The ISE and microhardness testing revealed statistically significant (ρ ≤ 0.05) dissolution inhibition and remineralisation potential for tooth sample treated with acidified 2%PGGA. From the FT-IR spectra, it was observed that the profiles of the enamel and HAp surfaces treated with 1%-and 2%-PGGA solutions were similar to those of PGGA powder.It was found that the viscosity of PGGA increases with increasing concentration. CONCLUSION: The study implies that 2% PGGA is more effective than NaF as forms a coating layer to protect from demineralisation and promote remineralisation of the tooth surface.


Assuntos
Esmalte Dentário/efeitos dos fármacos , Ácido Poliglutâmico/farmacologia , Remineralização Dentária , Cariostáticos , Humanos , Técnicas In Vitro , Fluoreto de Sódio/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Desmineralização do Dente
4.
Chemosphere ; 237: 124437, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31356994

RESUMO

Fluoride is known to affect the inflammatory process and autoregulation of immune responses, but the molecular mechanism by which fluoride causes innate immune injury remain largely unknown. Also, studies on sodium fluoride (NaF)-caused alteration of TLR signaling are still lacking. In the present study, we examined the effects of NaF on the mRNA and protein expression levels of TLR2/MyD88 signaling pathway molecules in the mouse spleen by using the methods of qRT-PCR and Western blotting. Consequently, we elucidated the mechanism underlying the effects of NaF on innate immunity. Two hundred and forty ICR mice were randomly divided into 4 groups with intragastric administration of distilled water in the control group and 12, 24, 48 mg/kg of NaF treatment in the experiment groups for 42 days. The findings revealed that NaF impaired splenic innate immunity in mice via inactivation of TLR2/MyD88 signaling pathway. NaF-inactivated TLR2/MyD88 signaling pathway was identified by prominently downregulated mRNA and protein expression levels of TLR2/MyD88, IRAK4, IRAK1, TRAF6, TAK1, MKK4/MKK7 and c-Jun, which ultimately altered the expression levels of IL-1ß, IL-4, IL-6 and IL-8 to attenuate innate immunity.


Assuntos
Imunidade Inata/efeitos dos fármacos , Fator 88 de Diferenciação Mieloide/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fluoreto de Sódio/farmacologia , Baço/imunologia , Receptor 2 Toll-Like/metabolismo , Animais , Citocinas/sangue , Camundongos , Proteínas/análise , RNA Mensageiro/sangue , Baço/metabolismo
5.
Colloids Surf B Biointerfaces ; 181: 77-84, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31125921

RESUMO

The aim of the present study was to formulate toothpastes containing biosurfactants and either fungal chitosan or sodium fluoride and evaluate the cytotoxicity, antimicrobial action and inhibition potential against biofilm formed by Streptococcus mutans. Chitosan was extracted from the biomass of the fungus Mucorales. We tested biosurfactants produced by Pseudomonas aeruginosa UCP 0992 (PB), Bacillus metylotrophicus UCP 1616 (BB) and Candida bombicola URM 3718 (CB). Fractional inhibitory concentration analysis was performed to determine the type of interaction between the compounds. Six toothpaste were prepared, the active ingredients of which were the biosurfactants, chitosan or sodium fluoride. The cytotoxicity tests were performed using the 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay for the L929 (mouse fibroblast) and RAW 264.7 (mouse macrophage) cell lines. The toothpastes were tested with regard to pH, consistency and foaming capacity. The inhibition of biofilm was investigated by applying the toothpaste to biofilm formed in modified artificial saliva for 24 h at 37 °C in anaerobiosis. All substances had a minimum inhibitory concentration (MIC) for S. mutans. The combinations of CB and PB with chitosan had an additive effect against S. mutans, whereas BB combined with chitosan had an indifferent effect. The toothpastes were non-toxic. The formulations had pH around 9, spreading capacity between 8 and 17 mm and foaming capacity between 63 and 95%. All formulations inhibited the cellular viability of S. mutans in the biofilm, with similar results compared to the commercial toothpaste tested. The present results show that the formulations suggested are promising when compared to a commercial tooth paste.


Assuntos
Quitosana/farmacologia , Streptococcus mutans/efeitos dos fármacos , Tensoativos/farmacologia , Cremes Dentais/química , Cremes Dentais/farmacologia , Animais , Biofilmes/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Quitosana/isolamento & purificação , Fibroblastos/efeitos dos fármacos , Camundongos , Tamanho da Partícula , Células RAW 264.7 , Fluoreto de Sódio/química , Fluoreto de Sódio/isolamento & purificação , Fluoreto de Sódio/farmacologia , Propriedades de Superfície , Tensoativos/química , Tensoativos/isolamento & purificação , Cremes Dentais/isolamento & purificação
6.
Microsc Res Tech ; 82(7): 1065-1072, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30884045

RESUMO

The objective of this in vitro study was to analyze and compare the biomimetic remineralizing efficacy of the self-assembling peptide (P11-4) with agents containing casein phoshopeptide-amorhous calcium phosphate fluoride (CPP-ACFP) and sodium fluoride (NaF) on artificial caries lesions using DIAGNOdent and micro-computed tomography (µCT). Artificial enamel lesions were prepared on extracted impacted sound mandibular third molars. The samples were randomly allocated to four groups (n = 8): Group 1, P11-4 (Curodont Repair, Credentis AG, Switzerland); Group 2, CPP-ACFP (MI Varnish, GCCo., Japan); Group3, NaF (Duraphat Varnish, Colgate, Colgate-Palmolive, NY, USA); Group 4, artificial saliva (control). The agents were applied to demineralized surfaces according to manufacturers' instructions; all specimens were stored in artificial saliva for 1 month. Demineralization and remineralization on enamel surfaces were analyzed and quantified by DIAGNOdent (KaVo, Germany) and µCT (SkyScan1174, Belgium) for lesion depth/area/volume/mineral density (MD). The remineralization efficacy of the agents was evaluated by DIAGNOdent on 1st, 7th, 30th days and by µCT on 30th day. Data were statistically analyzed by ANOVA, Kruskal-Wallis, T test, and Wilxocon tests. The highest remineralization efficacy findings in all periods were determined in Group 1, followed by Groups 2, 3, and 4. The remineralization findings for fluorescence, MD, lesion depth in Group 1 were found significantly higher (p < 0.01) than Group 3; and no significant differences (p > 0.05) were found between Groups 1-2 and Groups 2-3. The area and volume change values in Groups 1, 2, and 3 have shown no significancy (p > 0.05). A significant correlation (p < 0.01) was found between µCT and DIAGNOdent methods. The data of this study have demonstrated that P11-4 has showed the best remineralization efficacy, followed by CPP-ACFP and NaF. It is concluded that self-assembling peptide-based remineralization agent can be used successfully for biomimetic remineralization of enamel subsurface lesions.


Assuntos
Materiais Biomiméticos/farmacologia , Esmalte Dentário/efeitos dos fármacos , Esmalte Dentário/patologia , Peptídeos/farmacologia , Remineralização Dentária/métodos , Materiais Biomiméticos/química , Caseínas/farmacologia , Cárie Dentária , Fluoretos Tópicos , Humanos , Dente Molar/efeitos dos fármacos , Fluoreto de Sódio/farmacologia , Microtomografia por Raio-X
7.
Acta Odontol Scand ; 77(6): 419-425, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30905242

RESUMO

Objective: The objective of this study was to compare the remineralizing effect of sodium fluoride (NaF) mouth rinse or NaF gel as an adjunct to NaF dentifrice on incipient caries-like lesions in an in situ cross-over design study, with three sessions of 30 days each. Materials and methods: Orthodontic brackets with artificial demineralized enamel slabs were attached to the upper first molars of 12 participants. A set of 3 test specimens from the same tooth was randomly assigned to each participant and allocated into three 30-day sessions: 1) brushing with 0.22% NaF dentifrice 2 times/day (F dentifrice), 2) brushing with 0.22% NaF dentifrice 2 times/day+ rinsing with 0.05% NaF before bedtime (F mouth rinse), 3) brushing with 0.22% NaF dentifrice 2 times/day + brushing with 1.1% NaF gel before bedtime (F brush-on gel). The mineral gain and lesion depth of the specimens were evaluated by micro-computed tomography. Results: The mean mineral gain from the NaF mouth rinse and the NaF brush-on gel was similar, but greater than that from the NaF dentifrice (p < .05). The NaF brush-on gel yielded the greatest mean depth of remineralization (168 µm), followed by the NaF mouth rinse (144 µm). Both depths were significantly greater than that of the NaF dentifrice (84 µm) (p < .05). Conclusions: Both 0.05% NaF mouth rinse and 1.1% NaF brush-on gel, used at bedtime, increased incipient caries-like lesion remineralization in situ in combination with brushing with NaF dentifrice twice a day.


Assuntos
Cariostáticos/farmacologia , Cárie Dentária , Dentifrícios , Fluoreto de Sódio/farmacologia , Remineralização Dentária/métodos , Cremes Dentais , Microtomografia por Raio-X/métodos , Estudos Cross-Over , Fluoretos , Humanos , Minerais , Antissépticos Bucais
8.
Arch Oral Biol ; 99: 58-65, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30639774

RESUMO

OBJECTIVE: To determine the effect of pulpal perfusion on the fluid flow through human tooth after different treatments at the enamel surface. Changes in mineral density along with fluid flow rate were also analyzed before and after etching. DESIGN: The experiments were carried out on 97 human premolars. Ringer's solution and distilled water (DW) were applied under pressure of 20 mm Hg to the pulpal cavity of tooth crowns in the Ringer's-perfused and water-perfused groups respectively. Fluid flow through each specimen was recorded before and 0, 30, 60, 180 min after treatments at the enamel surface. The treatments included DW, 0.2% sodium fluoride solution, 1.23% acidulated phosphate fluoride gel (APF), 2.26% fluoride varnish (FV), 37% phosphoric acid gel (Etch) and artificial saliva (AS). Mineral density of the enamel was evaluated using micro-computed tomography. RESULTS: In water-perfused group, fluid flow rates recorded after etching were significantly increased (p = 0.005) with the significant reduction of mineral density (p = 0.018) from baseline. A significant negative correlation was found (r = -0.78, p = 0.015). After FV, the percentage reduction from baseline was significant at 180 min (p = 0.003). In Ringer's-perfused group, etching immediately produced the greatest mean flow rate and subsequently returned to the baseline within 60 min after treatment (p < 0.001). There were approximately 40, 55, and 63% reductions of flow rates within 60 min after AS, APF and FV respectively. CONCLUSION: Under simulated pulpal pressure, enamel fluid involves the process of enamel remineralization, particularly after etching.


Assuntos
Esmalte Dentário/efeitos dos fármacos , Polpa Dentária/efeitos dos fármacos , Polpa Dentária/metabolismo , Líquido Dentinal/metabolismo , Dente Pré-Molar , Cariostáticos/farmacologia , Esmalte Dentário/patologia , Fluoretos/farmacologia , Fluoretos Tópicos/farmacologia , Humanos , Permeabilidade/efeitos dos fármacos , Ácidos Fosfóricos/farmacologia , Solução de Ringer/farmacologia , Saliva Artificial , Fluoreto de Sódio/farmacologia , Propriedades de Superfície , Remineralização Dentária , Microtomografia por Raio-X
9.
Biol Trace Elem Res ; 191(2): 419-425, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30600503

RESUMO

The effect of fluoride on osteoclasts is still controversial. In the past, researchers thought that the effects of fluoride on osteoclast and osteoblast formation occurred in a dose-dependent pattern. However, our previous in vitro study showed fluoride elicited a notably different effect on osteoclast formation. To further verify the relationship between fluoride and osteoclast formation in vivo, 60 male C57BL/6 mice were randomly divided into three groups: two treatment groups consuming water supplemented with 50 and 100 mg/L of fluoride, and a third control group with nonsupplemented water. Ion selective electrode method analysis was used to detect bone fluoride content, and the effects of fluoride on bone tissue were assessed with hematoxylin and eosin (HE) staining. Additionally, the expression of BGP and ALP were examined by Western blot analysis, and tartrate-resistant acid phosphatase (TRAP) was assessed with immunohistochemistry. Osteoclasts in bone tissue were identified with a combination method of TRAP staining and cell morphology assessment. Results showed increasing expression of BGP among treatment groups as fluoride exposure increased, and ALP expression in the 100 mg/L treatment group was significantly higher than that for both the 50 mg/L treatment and control groups. The number of osteoclasts in the 50 mg/L group was highest amongst the three groups, followed by the 100 mg/L treatment and then by the control group, with the latter showing significantly fewer osteoclasts than in either treatment group. These results suggest that fluoride enhances bone formation at increasing levels of fluoride exposure. However, the inverted U-curve association was found between fluoride exposure and osteoclast formation, with the higher dose of fluoride having slightly reduced osteoclast formation. The results from this study may provide key insights towards understanding the role of osteoclasts in the progression of skeletal fluorosis.


Assuntos
Fluoretos/farmacologia , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Animais , Biomarcadores , Western Blotting , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Fluoreto de Sódio/farmacologia , Fosfatase Ácida Resistente a Tartarato/metabolismo
10.
Clin Oral Investig ; 23(1): 273-284, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29721706

RESUMO

AIM: To evaluate the erosive preventive effect of toothpastes in permanent (PT) and deciduous teeth (dt). DESIGN: Enamel samples were divided into five groups (n = 20): G1: placebo toothpaste; G2: NaF toothpaste; G3: AmF-NaF-SnCl2 anti-erosion toothpaste; G4: SnF2-toothpaste; and G5: NaF anti-erosion toothpaste for children. The samples were exposed to five erosion-abrasion cycles (artificial saliva incubation; 3 min in 1% citric acid; 2 min in slurry, toothbrush abrasion, 50 strokes, 200 g). Surface microhardness (SMH), surface specular reflection intensity (SRI), and cumulative surface loss (CSL) were measured. Comparisons among toothpastes were evaluated using Kruskal-Wallis tests and comparisons between PT and dt were evaluated using Wilcoxon's rank sum test. RESULTS: G1 exhibited significantly lower SMH values in PT than the other toothpastes (p < 0.05), with no significant differences among the others groups. In dt, G1 and G4 exhibited significantly different values than the other groups (p < 0.05). G4 exhibited lower values of SRI in both types of teeth. Deciduous teeth presented significantly higher SRI than PT (p < 0.05), except for G3. Deciduous teeth generally presented higher CSL than PT, except for G3. CONCLUSIONS: Deciduous teeth were more prone to mineral loss than permanent teeth. G5 exhibited better efficacy for both teeth, while G3 exhibited a better preventive effect only for deciduous teeth. CLINICAL RELEVANCE: Erosive tooth wear prevalence in children is growing and deciduous teeth are more susceptible than permanent teeth. Considering this, it is important to know the preventive effect of different toothpastes in an initial erosion-abrasion model.


Assuntos
Erosão Dentária/prevenção & controle , Cremes Dentais/farmacologia , Dente Pré-Molar , Ácido Cítrico , Dentição Permanente , Dureza , Humanos , Técnicas In Vitro , Dente Molar , Saliva Artificial , Fluoreto de Sódio/farmacologia , Propriedades de Superfície , Compostos de Estanho/farmacologia , Dente Decíduo , Escovação Dentária
11.
Biol Trace Elem Res ; 187(2): 499-505, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29915883

RESUMO

Fluoride had been reported to damage the structure and function of testicular tissues and reproductive cells; however, the mechanisms underlying its toxicity remained unclear. Autophagy plays a key role in reproductive function. In this study, we aimed to investigate the effect of fluoride on autophagy in Sertoli cells. Sertoli cells were exposed to 0, 0.125, 0.25, and 0.5 mM NaF for 24 h. The results showed that fluoride exposure up-regulated Beclin1 and p62 mRNA and protein expression levels with concomitant down-regulated mRNA and protein expression levels of LC3 and Atg5. In conclusion, exposure to fluoride impaired the autophagy process in Sertoli cells, which could be one of fluoride's mechanisms in male reproductive toxicity.


Assuntos
Apoptose/efeitos dos fármacos , Células de Sertoli/citologia , Células de Sertoli/efeitos dos fármacos , Fluoreto de Sódio/farmacologia , Animais , Relação Dose-Resposta a Droga , Masculino , Camundongos , Camundongos Endogâmicos
12.
Biol Trace Elem Res ; 189(1): 157-171, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30062462

RESUMO

At present, no reports are focused on fluoride-induced hepatic inflammatory responses in human beings and animals. This study aimed to investigate the mRNA and protein levels of inflammatory cytokines and signaling molecules for evaluating the effect of different doses (0, 12, 24, and 48 mg/kg) of sodium fluoride (NaF) on inflammatory reaction in the mouse liver by using methods of experimental pathology, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot analysis. We found that NaF in excess of 12 mg/kg caused the hepatic inflammatory responses, and the results showed that NaF activated the mitogen-activated protein kinases (MAPKs) signaling pathway by markedly increasing (p < 0.01 or p < 0.05) mRNA and protein levels of apoptosis signal-regulating kinase 1 (ASK1), mitogen-activated protein kinase kinases 1/2 (MEK1/2), extracellular signal-regulated protein kinases 1/2 (Erk1/2), mitogen-activated protein kinase kinases 4/7 (MEK4/7), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38) and mitogen-activated protein kinase kinases 3/6 (MEK3/6), and the nuclear factor-kappa B (NF-κB) signaling pathway by increasing (p < 0.01 or p < 0.05) the production of NF-κB and inhibitor of nuclear factor kappa-B kinase subunit beta (IKK-ß) and reducing (p < 0.01 or p < 0.05) the production of the inhibitory kappa B (IκB). Thus, NaF that caused the hepatic inflammatory responses was characterized by increasing (p < 0.01 or p < 0.05) the production of pro-inflammatory mediators such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemotactic protein 1 (MCP-1), and cyclooxygenase-2 (COX-2) via the activation of MAPKs and NF-κB pathways, and by significantly inhibiting (p < 0.01 or p < 0.05) the production of anti-inflammatory mediators including interleukin-4 (IL-4) and transforming growth factor beta (TGF-ß).


Assuntos
Citocinas/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Fluoreto de Sódio/farmacologia , Animais , Camundongos , Distribuição Aleatória , Transdução de Sinais/efeitos dos fármacos
13.
Environ Toxicol ; 34(1): 37-47, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30259626

RESUMO

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


Assuntos
Proliferação de Células/efeitos dos fármacos , Inibidor p16 de Quinase Dependente de Ciclina/genética , Metilação de DNA , Osteoblastos/efeitos dos fármacos , Fluoreto de Sódio/farmacologia , Adulto , Doenças Ósseas/sangue , Doenças Ósseas/induzido quimicamente , Doenças Ósseas/genética , Doenças Ósseas/urina , Divisão Celular/efeitos dos fármacos , Divisão Celular/genética , Proliferação de Células/genética , Células Cultivadas , Pré-Escolar , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Metilação de DNA/efeitos dos fármacos , Metilação de DNA/genética , Feminino , Fluoretos , Expressão Gênica/efeitos dos fármacos , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Masculino , Osteoblastos/fisiologia , Regiões Promotoras Genéticas/efeitos dos fármacos , Fluoreto de Sódio/urina , Adulto Jovem
14.
Equine Vet J ; 51(3): 375-383, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30218449

RESUMO

BACKGROUND: Early and accurate detection of stress remodelling in racehorses is of utmost importance to prevent catastrophic injuries. Current imaging techniques have limitations in assessing early changes predisposing to catastrophic breakdowns. Positron emission tomography (PET) using 18 F-sodium fluoride (18 F-NaF) is a sensitive method for the detection of early bone turnover and may improve early recognition of subtle injuries. OBJECTIVES: To validate the clinical use of 18 F-NaF PET in Thoroughbred racehorses, to assess the value of PET in the detection of bone lesions and to compare PET results with findings of other advanced imaging modalities, clinical examination and pathology. STUDY DESIGN: Experimental exploratory study. METHODS: Twenty fetlocks from nine Thoroughbred racehorses were imaged using 18 F-NaF PET, computed tomography (CT) and scintigraphy. Five fetlocks were also imaged with magnetic resonance imaging and four fetlocks were also examined histologically. Imaging findings were independently reviewed by three board certified radiologists. Imaging, clinical and histopathological findings were correlated. RESULTS: PET imaging was well-tolerated by all horses. PET detected focal areas of 18 F-NaF uptake in instances where other imaging modalities did not identify abnormalities, in particular in the proximal sesamoid bones. Maximal standardised uptake values could be measured to quantify the activity of lesions. Areas of 18 F-NaF uptake corresponded to regions of increased vascularity and increased osteoblastic activity. MAIN LIMITATIONS: Limited number of cases. CONCLUSIONS: 18 F-NaF PET imaging of the Thoroughbred fetlock is feasible and compares favourably with other imaging modalities in detecting stress remodelling in Thoroughbred racehorses. PET appears to be a beneficial imaging modality when used for early detection of stress remodelling in an effort to prevent catastrophic musculoskeletal injuries in this population of horses.


Assuntos
Cavalos , Articulações/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/veterinária , Compostos Radiofarmacêuticos/farmacologia , Fluoreto de Sódio/farmacologia , Animais , Membro Anterior , Membro Posterior , Coxeadura Animal/diagnóstico , Imagem por Ressonância Magnética , Cintilografia , Tomografia Computadorizada por Raios X
15.
Clin Oral Investig ; 23(6): 2583-2591, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30315423

RESUMO

OBJECTIVE: The aim of this study was to evaluate microbiological changes, oral soft tissue toxicity, and caries-preventive effect of an experimental titanium tetrafluoride (TiF4) varnish compared with a commercially available fluoride varnish (NaF), using in situ and in vivo models. MATERIALS AND METHODS: The treatment groups were the following: TiF4 varnish (experimental varnish), Duraphat® (fluoride positive control), placebo varnish (no fluoride), and no treatment (negative control). The varnishes were applied once over the enamel surface using a microbrush. For the in vivo study, 48 Wistar rats were infected with Streptococcus sobrinus 6715, received a treatment, and were submitted to a cariogenic challenge. After 4 weeks, S. sobrinus, oral soft tissue toxicity, presence, and severity of caries were evaluated. For the in situ study, 12 volunteers took part in this randomized crossover, double-blind study performed in four phases of 14 days each. They used intraoral appliances containing four enamel specimens that received the varnish according treatment group. After 24 h, the varnish was removed and plaque accumulation was allowed. A 20% sucrose solution was dripped over the enamel blocks (10×/day for 5 min each). Total streptococci, S. mutans, Lactobacillus, Candida spp. counts, and presence of white spot lesions were evaluated. Lesion depth was also quantified by micro-CT. RESULTS: For the in vivo study, the fluoride (F-varnishes) showed a statistically significant reduction in the percentage of S. sobrinus compared to the negative control (p < 0.05). Toxicological analysis revealed no abnormalities in oral tissues of rats from all groups, and both F-varnishes reduced the number and severity of caries lesions, without significant differences (p < 0.05). No statistical differences in microbiological counts were seen for the in situ experiment (p > 0.05). However, the specimens treated with TiF4 exhibited lower percentage of white spot lesions and the lesion depth was significantly reduced by F-varnishes (p < 0.05). CONCLUSIONS: F-varnishes showed reduction in the percentage of S. sobrinus in vivo, no oral soft tissue toxicity, and a caries-preventive effect in vivo and in situ. CLINICAL RELEVANCE: NaF varnish is largely used due its capacity to form CaF2-like layer on enamel. Therefore, development of studies focused on other fluoride compounds such as a TiF4 varnish, which may have greater efficacy than NaF against tooth demineralization, is important.


Assuntos
Cariostáticos/farmacologia , Cárie Dentária/prevenção & controle , Fluoretos/farmacologia , Titânio/farmacologia , Animais , Estudos Cross-Over , Método Duplo-Cego , Feminino , Fluoretos Tópicos/farmacologia , Humanos , Ratos , Ratos Wistar , Fluoreto de Sódio/farmacologia
16.
Clin Oral Investig ; 23(5): 2489-2496, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30306335

RESUMO

OBJECTIVE: The aim of the present in vitro study was to evaluate the remineralizing effects of NaF, AmF, KF gels and NaF toothpaste in combination with a potentially demineralizing saliva substitute (Glandosane; pH = 5.1) being widely used in Germany. METHODS: In each of 120 dentin specimens, three artificial lesions were created. One lesion was covered for analysis of pre-demineralization (ΔZB). Treatments during pH cycling (3 × 1 h demineralization/day [pH = 5.0] and 3 × 3 h Glandosane/day; 12 h 100%humidity) were as follows: no treatment (NT), application (5 min,2×/day) of 12.500 ppm F- [pH = 6.04] (NaF-gel1), 12.500 ppm F- [pH = 7.34] (NaF-gel2), 12.500 ppm F- [pH = 5.82] (AmF-gel), 1450 ppm F- [pH = 7.35] (KF-gel), and 5000 ppm F- [pH = 8.14]; (NaF-TP) for 7 days (E1). Subsequently, from each specimen, one lesion was covered, while the remaining lesion was cycled for another 7 days (E2). Differences in integrated mineral loss (ΔΔZE1/ΔΔZE2) were calculated between values before and after pH cycling. RESULTS: Mean (95%CI) ΔZB was 3851 (3762;3939) vol% × µm. Except for NaF-gel2 and NaF-TP, specimens of all other groups further demineralized. Only NaF-gel2 induced a significant gain in mineral content (p ≤ 0.004; paired t test). Significant differences in the change of mineral loss were found between NT and all fluoride groups for both ΔΔZE1 and for ΔΔZE2 (p < 0.05, Bonferroni post hoc test). However, only NaF-gel2 and NaF-TP induced remineralization. CONCLUSION: Under the in vitro conditions chosen, all fluoride agents could significantly hamper the adverse effects of a demineralizing saliva substitute. CLINICAL SIGNIFICANCE: In combination with a demineralizing saliva substitute, slight mineral gain was only observed for neutral NaF-gel2 and 5000 ppm F- toothpaste.


Assuntos
Cariostáticos/farmacologia , Dentina/efeitos dos fármacos , Fluoretos/farmacologia , Saliva/química , Remineralização Dentária , Cremes Dentais/farmacologia , Animais , Bovinos , Géis , Alemanha , Fluoreto de Sódio/farmacologia
17.
Arch Oral Biol ; 97: 91-96, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30368202

RESUMO

OBJECTIVE: The aim of this study was to investigate the effects of sodium fluoride (NaF) and amine fluoride (AmF) on bacterial viability in the oral cavity. MATERIAL AND METHODS: Healthy subjects brushed their teeth with either fluoride free toothpaste, NaF- or AmF-containing toothpaste. Biofilm smears from different locations were collected before and immediately and 30 and 120 min after tooth brushing. The smears were stained with live/dead bacterial staining, and the number of the respective bacteria was counted. The data were statistically analyzed by comparing the numbers of bacteria before and after the application of no fluoride, NaF and AmF. RESULTS: The highest numbers of bacteria were found in the tongue biofilm, followed by the palatal and cheek biofilm. The lowest numbers were found in the mouth floor biofilm. After the application of AmF, no changes in the numbers of bacteria were found in the biofilms, except for the cheek, where they were reduced. After the application of NaF, the number of bacteria decreased significantly in all biofilms. After 120 min, bacterial regrowth was complete. CONCLUSIONS: AmF has only little effect on the bacterial viability of oral biofilms. NaF application reduces the number of living bacteria in the oral biofilms. This effect lasts not longer than 120 min.


Assuntos
Aminas/farmacologia , Biofilmes/efeitos dos fármacos , Cariostáticos/farmacologia , Viabilidade Microbiana/efeitos dos fármacos , Fluoreto de Sódio/farmacologia , Escovação Dentária , Adulto , Contagem de Colônia Microbiana , Feminino , Voluntários Saudáveis , Humanos , Masculino , Microscopia de Fluorescência , Fatores de Tempo
18.
Mol Cell Biochem ; 454(1-2): 77-85, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30519783

RESUMO

Fluorosis and bone pathologies can be caused by chronic and/or excessive fluoride intake. Despite this, few studies have been conducted on the cellular mechanisms underlying osteoblast toxicity in the presence of NaF. Here, we investigated the effects of fluoride on MC3T3-E1 cells. We showed that the proliferation of MC3T3-E1 cells was inhibited by exposure to NaF. In addition, apoptosis was induced by NaF, as caspase-associated proteins showed a higher level of expression and apoptotic bodies were formed. Furthermore, endoplasmic reticulum (ER) stress induced by NaF activated the unfolded protein response (UPR) and upregulated the expression of the glucose-regulated proteins 94 (GRP94) and 78 (BiP). Therefore, ER stress plays a vital role in NaF-induced autophagy and apoptosis. Furthermore, apoptosis is promoted following the inhibition of NaF-induced autophagy. In conclusion, under NaF treatment, the ER stress-signaling pathway is activated, leading to apoptosis and autophagy and affecting the proliferation and survival of MC3T3-E1 cells.


Assuntos
Apoptose , Autofagia , Estresse do Retículo Endoplasmático , Osteoblastos/efeitos dos fármacos , Fluoreto de Sódio/toxicidade , Animais , Linhagem Celular , Camundongos , Osteoblastos/fisiologia , Transdução de Sinais , Fluoreto de Sódio/farmacologia , Resposta a Proteínas não Dobradas
19.
Arch Oral Biol ; 97: 245-252, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30414560

RESUMO

OBJECTIVES: This study evaluated the level and mechanism of apoptosis in human gingival fibroblasts (HGF) and murine fibroblasts (NIH/3T3) treated with a titanium tetrafluoride (TiF4) varnish compared those treated with a sodium fluoride (NaF) varnish. METHODS: Cells were treated with a TiF4, NaF (both 2.45%F) or placebo varnish for 6 h and were then examined using the TUNEL method. The activities of caspase-3, -8 and -9 were assessed. cDNA for Bax, Bad, Bcl-2 and Fas-L was amplified by quantitative PCR. Bax, Bcl-2 and Fas-L were further detected by western blot analysis. RESULTS: Both fluorides similarly increased the percentage of apoptosis, while they failed to activate caspases. The Bax/Bcl-2 gene expression ratio was not altered by either fluoride treatment regardless of the type of cell. NaF varnish increased the amplification of the Fas-L gene in NIH/3T3 and HGF cells, while treatment with the TiF4 varnish resulted in a lower Bad/Bcl-2 expression ratio compared to that of the control for NIH/3T3 cells, but not for HGF cells. No effect of the fluorides was detected in the protein analysis. CONCLUSIONS: NaF and TiF4, at the studied conditions, similarly induce a low level of apoptosis, with consequent modest activation of the Bcl-2 and Fas-l-dependent signalling pathways. Generally, HGF cells are more susceptible to the fluoride effect than NIH/3T3 cells.


Assuntos
Apoptose/efeitos dos fármacos , Cariostáticos/farmacologia , Fibroblastos/efeitos dos fármacos , Fluoretos/farmacologia , Fluoreto de Sódio/farmacologia , Titânio/farmacologia , Animais , Western Blotting , Caspases/metabolismo , Humanos , Marcação In Situ das Extremidades Cortadas , Camundongos , Células NIH 3T3 , Reação em Cadeia da Polimerase , Fatores de Tempo
20.
Biol Trace Elem Res ; 191(1): 189-198, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30565018

RESUMO

Increasing evidence has suggested an important role played by reactive oxygen species (ROS) in the pathogenesis of fluorosis. Accumulating evidence demonstrates that vitamin C administration ameliorate sodium fluoride (NaF)-induced oxidative stress. However, the potentially beneficial effects of vitamin C against NaF-induced cytotoxicity and the underlying molecular mechanisms of this protection are not fully understood. Here, we found that NaF stimulated cytotoxicity, increased mitochondrial reactive oxygen species (mROS) production, and induced apoptosis in F9 embryonic carcinoma cells. Consistent with this finding, NaF exposure was associated with decreased Sirtuin 1 (Sirt1) protein expression, thus promoted the acetylation of manganese superoxide dismutase (SOD2), a key enzyme involved in regulating mROS production. However, all NaF-induced mitochondrial oxidative injuries were efficiently ameliorated by overexpression of Sirt1 or incubation with Mito-TEMPO (a SOD2 mimetic). Moreover, pretreatment with vitamin C enhanced the expression of Sirt1 and decreased NaF-induced mitochondrial oxidative stress and apoptosis. Knockdown of Sirt1 blocked the vitamin C-mediated reduction in mROS and apoptosis via inhibiting Sirt1-SOD2 signaling. Importantly, sodium-dependent vitamin C transporter 2 (SVCT-2) siRNA was found to partially block the ability of vitamin C to promote Sirt1/SOD2 signaling. In summary, our data indicate that Sirt1 plays a pivotal role in the ability of vitamin C to stimulate SOD2 activity and attenuate mitochondrial oxidative stress, which partially through vitamin C receptor in NaF-induced F9 cells injury.


Assuntos
Apoptose/efeitos dos fármacos , Ácido Ascórbico/farmacologia , Mitocôndrias/enzimologia , Proteínas de Neoplasias/metabolismo , Neoplasias Embrionárias de Células Germinativas/enzimologia , Estresse Oxidativo/efeitos dos fármacos , Sirtuína 1/metabolismo , Fluoreto de Sódio/farmacologia , Superóxido Dismutase/metabolismo , Animais , Linhagem Celular Tumoral , Camundongos , Mitocôndrias/patologia , Neoplasias Embrionárias de Células Germinativas/patologia , Transdução de Sinais/efeitos dos fármacos
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