In vivo effect of fluoride combined with amoxicillin on enamel development in rats

Abstract Some evidence in vitro suggested that amoxicillin and fluoride could disturb the enamel mineralization. Objective: To assess the effect of amoxicillin and of the combination of amoxicillin and fluoride on enamel mineralization in rats. Methodology: In total, 40 rats were randomly assigned to four groups: control group (CG); amoxicillin group (AG - amoxicillin (500 mg/kg/day), fluoride group (FG - fluoridated water (100 ppm -221 mg F/L), and amoxicillin + fluoride group (AFG). After 60 days, the samples were collected from plasma and tibiae and analyzed for fluoride (F) concentration. The incisors were also collected to determine the severity of fluorosis using the Dental Fluorosis by Image Analysis (DFIA) software, concentration of F, measurements of enamel thickness, and hardness. The data were analyzed by ANOVA, Tukey's post-hoc test, or Games-Howell post-hoc test (α=0.05). Results: Enamel thickness of the incisors did not differ statistically among the groups (p=0.228). Groups exposed to fluoride (AFG and FG) have higher F concentrations in plasma, bone and teeth than those not exposed to fluoride (CG and AG). The groups showed a similar behavior in the DFIA and hardness test, with the FG and AFG groups showing more severe fluorosis defects and significant lower hardness when compared with the AG and CG groups, with no difference from each other. Conclusion: The rats exposed to fluoride or fluoride + amoxicillin developed dental fluorosis, while exposure to amoxicillin alone did not lead to enamel defects.

Liver proteome of mice with different genetic susceptibilities to the effects of fluoride

ABSTRACT A/J and 129P3/J mice strains have been widely studied over the last few years because they respond quite differently to fluoride (F) exposure. 129P3/J mice are remarkably resistant to the development of dental fluorosis, despite excreting less F in urine and having higher circulating F levels. These two strains also present different characteristics regardless of F exposure. Objective In this study, we investigated the differential pattern of protein expression in the liver of these mice to provide insights on why they have different responses to F. Material and Methods Weanling male A/J and 129P3/J mice (n=10 from each strain) were pared and housed in metabolic cages with ad libitum access to low-F food and deionized water for 42 days. Liver proteome profiles were examined using nLC-MS/MS. Protein function was classified by GO biological process (Cluego v2.0.7 + Clupedia v1.0.8) and protein-protein interaction network was constructed (PSICQUIC, Cytoscape). Results Most proteins with fold change were increased in A/J mice. The functional category with the highest percentage of altered genes was oxidation-reduction process (20%). Subnetwork analysis revealed that proteins with fold change interacted with Disks large homolog 4 and Calcium-activated potassium channel subunit alpha-1. A/J mice had an increase in proteins related to energy flux and oxidative stress. Conclusion This could be a possible explanation for the high susceptibility of these mice to the effects of F, since the exposure also induces oxidative stress.

Efeito da ingestão crônica do fluoreto sobre o sistema oxidante/antioxidante de ratos / Effect of chronic fluoride intake in the oxidant/antioxidant system of rats

A ingestão excessiva de fluoreto por um longo período de tempo pode resultar em fluorose, que pode causar manifestações dentárias e esqueléticas. Danos metabólicos, funcionais e estruturais causados pela fluorose crônica tem sido relatados em vários tecidos. O objetivo deste estudo foi avaliar os efeitos do fluoreto administrado na água de beber, da administração de fluoreto na água de beber na defesa antioxidante de ratos. Quatro grupos de ratos wistar foram usados (n=10/grupo). Os animais receberam água de beber contendo 0 (controle), 5, 15 ou 50 ppm de fluoreto durante 60 dias. Eles foram eutanasiados e os tecidos (fígado, rins e coração) e plasma foram coletados e homogenizados. Superóxido dismutase (SOD), catalase (CAT), glutationa peroxidase (GPx), glutationa reduzida (GSH), substâncias antioxidantes totais (SAT), substâncias reativas ao ácido tiobarbitúrico (TBARS), hidroperóxido de lipídios (HL) e fluoreto foram análisadas. Dados foram analisados por ANOVA e teste de Tukey ou Kruskal-Wallis e teste de Dunn (p<0,05). Nos rins, SOD, GPx, GSH e SAT diminuiram e fluoreto e HL aumentaram significantivamente. No fígado, CAT e TBARS diminuiram, SOD, HL e SAT aumentaram significativamente. No coração, GPx aumentou significativamente. No plasma, SOD e HL diminuiram significativamente. Em resumo, esses resultados mostram que a administração crônica de fluoreto altera o sistema antioxidante de ratos. Nosso dados sugerem que a exposição em níveis elevados de fluoreto, a conversão do ânion superóxido em água nos rins parecem ocorrer principalmente através da SOD e CAT, com baixa participação do sistema glutationa, diferindo do que parece ocorrer no fígado.

Excessive fluoride intake over a long period of time could result in fluorosis, which can lead to dental and skeletal manifestations. Metabolic, functional and structural damages caused by chronic fluorosis have been reported in many tissues. The aim of this study was to evaluate the effect of fluoride, administered in drinking water, in the antioxidant defense of rats. Four groups of Wistar rats were included (n=10/group). The animals received drinking water containing 0 (control), 5, 15 or 50 ppm of fluoride during 60 days. They were euthanized and the tissues (liver, kidney and heart) and plasma were collected and homogenized. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), antioxidants, thiobarbituric acid reactive substances (TBARS), lipid hydroperoxide (LH), and fluoride were analyzed. Data were analyzed by ANOVA and Tukeys test or Kruskal-Wallis and Dunns tests (p<0.05). In the kidney SOD, GPx, GSH and SAT decreased and fluoride and LH increased significantly. In the liver, CAT and TBARS decreased and fluoride, SOD, LH and SAT increased significantly. In the heart, GPx increased significantly. In the plasma, SOD and LH decreased significantly. In summary, these results show that chronic fluoride administration alters the antioxidant system of the rats. Our data suggest that upon exposure to high levels of fluoride, the conversion of the superoxide anion to water in the kidney seems to occur mainly through the SOD and CAT, with a low participation of the glutathione system, differing from what seems to occur in the liver.

Efeito da ingestão crônica do fluoreto sobre o sistema oxidante/antioxidante de ratos / Effect of chronic fluoride intake in the oxidant/antioxidant system of rats

A ingestão excessiva de fluoreto por um longo período de tempo pode resultar em fluorose, que pode causar manifestações dentárias e esqueléticas. Danos metabólicos, funcionais e estruturais causados pela fluorose crônica tem sido relatados em vários tecidos. O objetivo deste estudo foi avaliar os efeitos do fluoreto administrado na água de beber, da administração de fluoreto na água de beber na defesa antioxidante de ratos. Quatro grupos de ratos wistar foram usados (n=10/grupo). Os animais receberam água de beber contendo 0 (controle), 5, 15 ou 50 ppm de fluoreto durante 60 dias. Eles foram eutanasiados e os tecidos (fígado, rins e coração) e plasma foram coletados e homogenizados. Superóxido dismutase (SOD), catalase (CAT), glutationa peroxidase (GPx), glutationa reduzida (GSH), substâncias antioxidantes totais (SAT), substâncias reativas ao ácido tiobarbitúrico (TBARS), hidroperóxido de lipídios (HL) e fluoreto foram análisadas. Dados foram analisados por ANOVA e teste de Tukey ou Kruskal-Wallis e teste de Dunn (p<0,05). Nos rins, SOD, GPx, GSH e SAT diminuiram e fluoreto e HL aumentaram significantivamente. No fígado, CAT e TBARS diminuiram, SOD, HL e SAT aumentaram significativamente. No coração, GPx aumentou significativamente. No plasma, SOD e HL diminuiram significativamente. Em resumo, esses resultados mostram que a administração crônica de fluoreto altera o sistema antioxidante de ratos. Nosso dados sugerem que a exposição em níveis elevados de fluoreto, a conversão do ânion superóxido em água nos rins parecem ocorrer principalmente através da SOD e CAT, com baixa participação do sistema glutationa, diferindo do que parece ocorrer no fígado.

Excessive fluoride intake over a long period of time could result in fluorosis, which can lead to dental and skeletal manifestations. Metabolic, functional and structural damages caused by chronic fluorosis have been reported in many tissues. The aim of this study was to evaluate the effect of fluoride, administered in drinking water, in the antioxidant defense of rats. Four groups of Wistar rats were included (n=10/group). The animals received drinking water containing 0 (control), 5, 15 or 50 ppm of fluoride during 60 days. They were euthanized and the tissues (liver, kidney and heart) and plasma were collected and homogenized. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), antioxidants, thiobarbituric acid reactive substances (TBARS), lipid hydroperoxide (LH), and fluoride were analyzed. Data were analyzed by ANOVA and Tukeys test or Kruskal-Wallis and Dunns tests (p<0.05). In the kidney SOD, GPx, GSH and SAT decreased and fluoride and LH increased significantly. In the liver, CAT and TBARS decreased and fluoride, SOD, LH and SAT increased significantly. In the heart, GPx increased significantly. In the plasma, SOD and LH decreased significantly. In summary, these results show that chronic fluoride administration alters the antioxidant system of the rats. Our data suggest that upon exposure to high levels of fluoride, the conversion of the superoxide anion to water in the kidney seems to occur mainly through the SOD and CAT, with a low participation of the glutathione system, differing from what seems to occur in the liver.

Physiology and toxicity of fluoride.

Fluoride has been described as an essential element needed for normal development and growth of animals and extremely useful for human beings. Fluoride is abundant in the environment and the main source of fluoride to humans is drinking water. It has been proved to be beneficial in recommended doses, and at the same time its toxicity at higher levels has also been well established. Fluoride gets accumulated in hard tissues of the body and has been know to play an important role in mineralization of bone and teeth. At high levels it has been known to cause dental and skeletal fluorosis. There are suggested effects of very high levels of fluoride on various body organs and genetic material. The purpose of this paper is to review the various aspects of fluoride and its importance in human life.

Decreased intelligence in children and exposure to fluoride and arsenic in drinking water

Recent evidence suggests that fluoride (F) and arsenic (As) may adversely affect intelligence quotient (IQ) scores. We explore the association between exposure to F and As in drinking water and intelligence in children. Three rural communities in Mexico with contrasting levels of F and As in drinking water were studied: Moctezuma (F 0.8±1.4mg/L; As 5.8±1.3µg/L); Salitral (F 5.3±0.9mg/L; As 169±0.9µg/L) and 5 de Febrero (F 9.4±0.9mg/L; As 194±1.3µg/L). The final study sample consisted of 132 children from 6 to 10 years old. After controlling for confounders, an inverse association was observed between F in urine and Performance, Verbal, and Full IQ scores (beta values = -13, -15.6, -16.9, respectively). Similar results were observed for F in drinking water (beta values = -6.7, -11.2, -10.2, respectively) and As in drinking water (beta values= -4.30, -6.40, -6.15, respectively). The p-values for all cases were < 0.001. A significant association was observed between As in urine and Full IQ scores (beta = -5.72, p = 0.003). These data suggest that children exposed to either F or As have increased risks of reduced IQ scores.

Estudios recientes sugieren que el flúor (F) y el arsénico (As) pueden tener efectos adversos sobre el coeficiente intelectual (CI). En este estudio exploramos la asociación entre el F y el As y la inteligencia en niños expuestos a estas sustancias a través del agua. Tres comunidades rurales de México con diferentes niveles de F y As fueron estudiadas: Moctezuma (F 0,8±1,4mg/L; As 5,8±1,3µg/L); Salitral (F 5,3±0,9mg/L; As 169±0,9µg/L) y 5 de Febrero (F 9,4±0,9mg/L; As 194±1,3µg/L). La muestra final fue de 132 niños de 6 a 10 años de edad. Después de controlar por confusores, se obtuvieron asociaciones inversas entre F en orina y las puntuaciones de los CI (Desempeño, Verbal y Total) (valores beta = -13, -15,6, -16,9, respectivamente) p < 0,001 en todos los casos. Resultados similares se obtuvieron con F en agua (valores beta = -6,7, -11,2, -10,2, respectivamente) y con As en agua (valores beta = -4,30, -6,40, -6,15, respectivamente). En todos los casos p < 0,001. Para As en orina, se obtuvo una asociación inversa con las puntuaciones del CI total (beta= -5,72; p = 0,003). Estos datos sugieren que los niños expuestos al F o al As tienen mayor riesgo de tener disminución en las puntuaciones del CI.

Potencial tóxico dos alginatos para uso odontológico / Potencial toxicity of dental alginates

O alginato ou hidrocolóide irreversível é um dos materiais de moldagem mais aceitos e utilizados na Odontologia. Muitas substâncias como zinco, cádmio, silicato de chumbo e fluoretos foram adicionadas em algumas marcas de alginatos, com o objetivo de melhorar suas propriedades físicas, químicas, mecânicas e se tornaram causa de preocupação no que se refere à toxicidade desses materiais. Em algumas marcas de alginatos relatou-se a presença de fluoretos, cádmio, silicatos de chumbo e zinco potencialmente tóxicos, isoladamente ou em conjunto, consequentemente, cuidados especiais devem ser tomados na preparação desses materiais. É necessário que haja um controle contínuo de metais e substâncias potencialmente tóxicas nos alginatos para se evitar a contaminação dos profissionais da área odontológica e pacientes. Nesta revisão analisou-se o potencial tóxico de alginatos usados em odontologia.

fluoridation controversy

Fluoridation of drinking water supply has been hailed as one of the top ten public health achievements of the twentieth century. At an optimal level of 1.0 ppm, it is considered the most cost-effective, safe and efficient strategy of reducing dental decay in all social strata of the community. The anticariogenic mechanism of fluoride does not differentiate between the benefits of topical fluoride or ingested fluoride. Fluoride toxicity leads to dental and skeletal fluorosis. The irreversible, debilitating effects of fluoride toxicity, the transient effects with the continuous need of exposure to fluoride to maintain caries resistance and the fact that benefits of topical use of fluoride are as good as ingested fluoride are some of the leading contributing factors that have sparked the fluoridation controversy. Anti-fluoride lobby claims range from declaring fluoride as a slow, cumulative poison to fluoridation of community drinking water as a violation of human rights. Adopting the precautionary principle categorizes fluoridation of community drinking water supply as an unreasonable risk. It is recommended to limit fluoride to dentifrices and mouthwashes

Neurotoxicity of fluoride: neurodegeneration in hippocampus of female mice.

Light microscopic study of hippocampal sub-regions demonstrated significant number of degenerated nerve cell bodies in the CA3, CA4 and dentate gyrus(Dg) areas of sodium fluoride administered adult female mice. Ultrastructural studies revealed neurodegenrative characteristics like involution of cell membranes, swelling of mitochondria, clumping of chromatin material etc, can be observed in cell bodies of CA3, CA4 and dentate gyrus (Dg). Fluoride intoxicated animals also performed poorly in motor co-ordination tests and maze tests. Inability to perform well increased with higher fluoride concentration in drinking water.

Knowledge and attitude of dental health workers towards fluoride in Riyadh area

To assess the knowledge, attitudes, and beliefs of the dentists and hygienists in the Riyadh area of the Kingdom of Saudi Arabia towards fluoride. One hundred and thirty dentists and hygienist working in dental clinics in Riyadh were randomly selected. Self-administered questionnaires covered the following areas: general information, the use and application of fluoride, pharmacodymanics and pharmacokinetics of fluoride. The subjects responded to each of the statements by ticking one of the 3-scaled options from "agree" to "disagree". The majority of the respondents [65%] supported an assessment of the pattern of dental caries before fluoridating the water, 23% disagreed and 5% did not know. Also one hundred and three [79%] of the sample supported fluoridation of water, 16 [12%] disagreed, and 4 [3%] did not know. Fifty-five [42%] agreed that dental caries are expected to increase if fluoridating water is discontinued for one year, while 52 [40%] disagreed and 16 [12%] did not know. In addition, there was a low score concerning knowledge of side effects and toxicity of fluoride among health care workers. Overall, there was no statistical significance between academics and non-academics. There was a good attitude and knowledge of fluoride as a preventive measure among dentists. This study also demonstrated that the majority of the health care professionals in Riyadh area were in favor of water and milk fluoridation, however; there was a lack of knowledge regarding side effects and toxicity

Prevençäo em odontopediatria: fluoretos: conceitos atuais e tedências futuras / Pediatric dentistry prevention: fluorides: actualities conceptions and futures trends

O presente trabalho teve por objetivo relatar os meios e métodos da utilizaçäo segura de fluoretos na prática odontológica visando a prevençäo e controle da cárie dentária no paciente infantil

Administración de fluoruros sistémicos y tópicos en niños preescolares / Systemic and topical fluorides administration in preschool children

El incuestionable valor del flúor como elemento anticariogénico ha llevado a la difusión de su uso masivo en todo el mundo, con resultados sumamente alentadores. Los últimos 40 años de investigación en ese campo se ven hoy reflejados en la salud bucal de los habitantes de muchos países. Harold Loe señala que en 1987 el 50 por ciento de 40.000 escolares de 5 a 17 años, no tenían experiencia de caries en U.S.A., lo que representa un gran incremento sobre el 37 por ciento hallado en 1980. La fluoración de las aguas de bebida, la administración de suplementos (comprimidos y gotas), los alimentos fluorados, los enjuagatorios, los geles o las pastas dentales fluoradas constituyen sus vehículos habituales. Todos ellos, producto de una cuidadosa evaluación, carecen en general de contraindicaciones en escolares, adolescentes y adultos. Sin embargo, cuando tratamos a preescolares, merecen algunas consideraciones especiales

A propósito de la genotoxicidad y cancerogénesis de los fluoruros / A propos of genotoxicity and cancerogenesis of fluorides

Los efectos de los fluoruros como agentes preventivos de las caries han sido rigurosamente establecidos. También se han empleado con éxito en el tratamiento de la osteoporosis. Todo indica que el uso de los fluoruros será cada vez mayor, por lo que se vuelve a replantear la pregunta relativa a la capacidad colateral de dañar la salud y en particular de aumentar el riesgo de cáncer. La revisión de la literatura muestra escasas investigaciones que planteen que los fluoruros tiene efectos genotóxicos y cancerogénicos; los artículos que lo han sostenido han sido fuertemente criticados por la comunidad científica especializada y considerados de limitado alcance por presentar serias dificultades metodológicas. El grueso de la información experimental y epidemiológica disponible evidencia que a la luz de los conocimientos contemporáneos no existen datos que demuestren que las concentraciones de fluoruros recomendadas para la prevención estomatológica aumenten el riesgo de cualquier enfermedad

Una mirada a la genotoxicología de los fluoruros / A look to genotoxicology of fluorides

Se presenta una revisión de la literatura en la que se detectó que los resultados de las investigaciones en relación con la capacidad potencial de los fluoruros de producir daño en los sistemas genéticos celulares, pueden ser agrupadas en 3 categorías: um grupo de investigadores sostiene que los fluoruros son agentes mutágenos capaces de dañar el DNA y los cromosomas; otros estiman que no tienen tales potencialidades genotóxicas y un último criterio sustentado por pocos trabajos experimentales, considera que poseen sinergismo o efectos antagónicos con algunos mutágenos conocidos. El análisis de los artículos publicados pone de manifestio que los polémicos resultados de la década del sesenta y setenta han ido aclarándose en la medida en que la genotoxicología se ha desarrollado como ciencia y han aparecido pruebas más precisas y confiables. Queda claro en la literatura que la exposición aguda a los fluoruros no causa alteraciones en los sistemas biológicos celulares en los que han sido realizadas las pruebas y que en el caso de la exposición crónica, los estudios más recientes y mejor diseñados coinciden en que no producen efectos deletéreos al nivel de las dosis empleadas en la prevención de la caries dental; pero en este aspecto, a juicio de algunos científicos, debe investigarse más para llegar a una conclusión definitiva

Algunas consideraciones en relación a la toxicidad de los fluoruros de aplicación odontológica / Some considerations related to toxicity of fluoride compounds used in dentistry

Se realiza una revisión bibliográfica para recopilar los conocimientos actuales en relación a toxicidad aguda y crónica de los comnpuestos fluorurados de uso odontológico, utilizados en la prevención de la caries dentaria. Se describen tratamientos de emergencia en caso de toxicidad aguda, como también los márgenes de seguridad de los compuestos utilizados en dosis bajas y por tiempos prolongados. Finaliza el trabajo con algunas conclusiones y recomendaciones encaminadas a disminuir los riesgos de intoxicación crónica o aguda por fluoruros