RESUMO
This review summarizes essential information about the chemical stability of NaYF4-based upconverting nanoparticles (UCNPs) in aqueous solutions, a crucial aspect for achieving high quality standards for biomedical materials. We present an in-depth analysis of the major experimental evidence and proposed mechanisms that provide a theoretical framework for understanding UCNPs degradation, destabilization, and dissolution under different conditions such as media composition, temperature, particle size, and the synthetic methods employed. The ion release and disintegration of the UCNP crystal structure may trigger cytotoxic events within living organisms and impact on their optical properties, precluding their safe use in biological environments. Also, we present a summary of the characterization techniques' toolbox employed for monitoring and detecting these degradation processes. Closing the existing "information gap" that links UCNP physicochemical properties, such as solubility and chemical stability, with the biological response of living organisms or tissues, is vital for using these nanoparticles as biological tracer probes, theranostic vehicles, or for clinical purposes. The understanding of chemical phenomena at the nanoparticle solid-liquid interface is mandatory to complete the molecular picture of nanosized objects, orienting in a rational manner the efforts of research and development in the early stages of these functional materials.
Assuntos
Fluoretos/metabolismo , Nanopartículas Metálicas/química , Ítrio/metabolismo , Animais , Linhagem Celular Tumoral , Estabilidade de Medicamentos , Fluoretos/química , Fluoretos/efeitos da radiação , Fluoretos/toxicidade , Humanos , Luz , Nanopartículas Metálicas/efeitos da radiação , Nanopartículas Metálicas/toxicidade , Fenômenos Ópticos , Ítrio/química , Ítrio/efeitos da radiação , Ítrio/toxicidadeRESUMO
Long-term exposure to high concentrations of fluoride (F) can damage mineralized and soft tissues such as bones, liver, kidney, intestine, and nervous system of adult rats. The high permeability of the blood-brain barrier and placenta to F during pregnancy and lactation may be critical to neurological development. Therefore, this study aimed to investigate the effects of F exposure during pregnancy and lactation on molecular processes and oxidative biochemistry of offspring rats' hippocampus. Pregnant Wistar rats were randomly assigned into 3 groups in accordance with the drinking water received: G1 - deionized water (control); G2 - 10 mg/L of F and G3 - 50 mg/L of F. The exposure to fluoridated water began on the first day of pregnancy and lasted until the 21st day of breastfeeding (when the offspring rats were weaned). Blood plasma samples of the offspring rats were collected to determine F levels. Hippocampi samples were collected for oxidative biochemistry analyses through antioxidant capacity against peroxyl (ACAP), lipid peroxidation (LPO), and nitrite (NO2-) levels. Also, brain-derived neurotrophic factor (BDNF) gene expression (RT-qPCR) and proteomic profile analyses were performed. The results showed that exposure to both F concentrations during pregnancy and lactation increased the F bioavailability, triggered redox imbalance featured by a decrease of ACAP, increase of LPO and NO2- levels, BDNF overexpression and changes in the hippocampus proteome. These findings raise novel questions regarding potential repercussions on the hippocampus structure and functioning in the different cognitive domains.
Assuntos
Poluentes Ambientais/toxicidade , Fluoretos/toxicidade , Hipocampo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Animais , Antioxidantes/metabolismo , Fator Neurotrófico Derivado do Encéfalo , Feminino , Fluoretos/metabolismo , Hipocampo/crescimento & desenvolvimento , Lactação , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Proteoma/metabolismo , Proteômica , Ratos , Ratos WistarRESUMO
Fluoride, a pollutant present in contaminated ground water, oral care products, food, and pesticides, has deleterious effects in the structure and function of the central nervous system. Among the established neurological defects described in the exposed population, a reduced score in intelligence quotient tests in children of contaminated areas has gained attention over the past years. Maternal fluoride exposure during gestation decreases learning and memory abilities that correlate with a significant diminution of glutamate receptors expression. Since the involvement of glia cells in the maintenance and regulation of glutamatergic synapses is well-documented, in this contribution, we characterized the effect of fluoride exposure in the regulation of glia glutamine transporters. To this end, we used the Müller glia cell line, Mio-M1, and through the use of [3H]L-Glutamine uptake experiments and a Western blot approach, we demonstrate here the functional expression of system N of glutamine transporters, SNAT3 and SNAT5, in this model of human retina radial glia cells. Furthermore, these transporters interact with the glutamate transporter excitatory amino acid transporter 1, in an activity-dependent manner. Fluoride treatment reduces glutamine uptake and cell membrane [3H]glutamine surface binding, in good correlation with a decrease in SNAT3 and 5 protein levels. These results demonstrate that glia cells respond to the presence of fluoride reducing glutamine mobilization and by these means decreases glutamate turnover suggesting a disruption of glutamatergic transmission.
Assuntos
Fluoretos/farmacologia , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Neuroglia/efeitos dos fármacos , Sistema X-AG de Transporte de Aminoácidos/metabolismo , Transporte Biológico/efeitos dos fármacos , Células Cultivadas/efeitos dos fármacos , Células Ependimogliais/efeitos dos fármacos , Fluoretos/metabolismo , Humanos , Receptores de Glutamato/metabolismo , Sinapses/metabolismoRESUMO
Water fluoridation is an important public health measure for the control of dental caries. Recent animal studies have shown that low doses of fluoride (F) in the drinking water, similar to those found in public water supplies, increase insulin sensitivity and reduce blood glucose. In the present study we evaluated the effects of low-level F exposure through the drinking water on glucose homeostasis in female NOD mice. Seventy-two 6-week mice were randomly divided into 2 groups according to the concentration of F in the drinking water (0-control, or 10 mg/L) they received for 14 weeks. After the experimental period the blood was collected for analyses of plasma F, glucose and insulin. Liver and gastrocnemius muscle were collected for proteomic analysis. Plasma F concentrations were significantly higher in the F-treated than in the control group. Despite treatment with fluoridated water reduced plasma levels glucose by 20% compared to control, no significant differences were found between the groups for plasma glucose and insulin. In the muscle, treatment with fluoridated water increased the expression of proteins related to muscle contraction, while in the liver, there was an increase in expression of antioxidant proteins and in proteins related to carboxylic acid metabolic process. Remarkably, phosphoenolpyruvate carboxykinase (PEPCK) was found exclusively in the liver of control mice. The reduction in PEPCK, a positive regulator of gluconeogenesis, thus increasing glucose uptake, might be a probable mechanism to explain the anti-diabetic effects of low doses of F, which should be evaluated in further studies.
Assuntos
Poluentes Ambientais/toxicidade , Fluoretos/toxicidade , Glucose/metabolismo , Homeostase/efeitos dos fármacos , Animais , Glicemia/análise , Cárie Dentária , Poluentes Ambientais/metabolismo , Feminino , Fluoretos/metabolismo , Gluconeogênese , Insulina/metabolismo , Resistência à Insulina , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos NOD , Músculo Esquelético/metabolismo , Proteômica , Testes de ToxicidadeRESUMO
This study aimed to evaluate the gastrointestinal absorption and renal excretion of fluoride after the ingestion of high-fluoride dentifrice. Twelve volunteers participated in this in vivo, crossover, and blinded study. In three experimental phases, the volunteers were randomly assigned to one of three treatment groups, who ingested either the following: distilled and deionized water (control), conventional dentifrice (1100 µg/g), or high-fluoride dentifrice (5000 µg/g). Both dentifrices contained fluoride in the form of NaF/SiO2. To determine the rate of fluoride absorption, non-stimulated saliva was collected for up to 120 min after ingestion and the area under the curve of the salivary fluoride concentration was plotted as a function of time and the maximum concentration determined. All urine produced during the 24 h before and after ingestion was collected, and urinary excretion was calculated from the difference between the urinary fluoride concentrations in the two periods. A specific ion electrode coupled to an ion analyzer was used to measure fluoride concentrations. Statistical analysis was performed by ANOVA followed by Tukey's test with p set at 5%. All measured parameters were highest after the ingestion of the dentifrice with 5000 µg/g (p < 0.001), confirming that this has an increased level of bioavailable fluoride compared with the conventional dentifrice. The high-fluoride dentifrice increases the concentration of salivary fluoride, which may explain its greater anticaries effect. However, it poses a potential risk of causing dental fluorosis and so should not be used by children.
Assuntos
Dentifrícios/química , Fluoretos/metabolismo , Fluoretos/urina , Absorção Gastrointestinal/fisiologia , Rim/metabolismo , Adulto , Estudos Cross-Over , Humanos , Saliva/química , Adulto JovemRESUMO
The present study investigated the effect of chronic exercise on fluoride (F) metabolism in fluorosis-susceptible mice exposed to high-F and explored the relationship between F concentrations in bone and plasma. Thirty male mice were randomised into three groups: Group I (No-F, No-Exercise), Group II (50 ppmF, No-Exercise), Group III (50 ppmF, Exercise). Body weight and physical performance of all mice were measured at baseline and end of experiment. F concentrations of plasma and bone were measured at the end of experiment. Mean plasma F concentration was significantly higher (p < 0.001) in Groups II and III compared with Group I. Mean bone F concentration was also significantly higher (p < 0.01) in Groups II and III compared with Group I. There was a significant correlation (p = 0.01, r = 0.54) between F concentration of plasma and bone. Mean body weight of Group I mice was significantly higher than Group II (p < 0.001) and Group III (p = 0.001) mice at the end of the experiment. This study, which provides the first data on the effect of chronic exercise on F metabolism in fluorosis-susceptible mice, suggests no effect of chronic exercise on F in plasma and bone. However, exposure to high-F resulted in lower body weight and exercise capacity in mice.
Assuntos
Fluoretos/metabolismo , Fluoretos/farmacologia , Condicionamento Físico Animal/fisiologia , Animais , Peso Corporal/efeitos dos fármacos , Osso e Ossos/química , Fluoretos/sangue , Fluorose Dentária , Masculino , Camundongos , Desempenho Físico FuncionalRESUMO
Since the classical epidemiological studies by Dean, it has been known that there should be an optimum level of exposure to fluoride that would be able to provide the maximum protection against caries, with minimum dental fluorosis. The "optimal" daily intake of fluoride for children (0.05-0.07 mg per kilogram bodyweight) that is still accepted worldwide was empirically determined. In the present review, we discuss the appropriateness of the current guidance for fluoride intake, in light of the windows of susceptibility to caries and fluorosis, the modern trends of fluoride intake from multiple sources, individual variations in fluoride metabolism, and recent epidemiological data. The main conclusion is that it is very difficult to think about a strict recommendation for an "optimal" range of fluoride intake at the individual level in light of existing knowledge of 1) the mechanisms of action of fluoride to control caries, 2) the mechanisms involved in dental fluorosis development, 3) the distinct factors that interfere in the metabolism of fluoride, and 4) the windows of susceptibility to both dental caries and fluorosis development. An "optimal" range of fluoride intake is, however, desirable at the population level to guide programs of community fluoridation, but further research is necessary to provide additional support for future decisions on guidance in this area. This list includes the effect of factors affecting fluoride metabolism, clinical trials on the effectiveness of low-fluoride dentifrices to prevent caries in the primary dentition, and validation of biomarkers of exposure to fluoride.
Assuntos
Cárie Dentária/prevenção & controle , Fluoretos/administração & dosagem , Guias de Prática Clínica como Assunto , Criança , Dentifrícios/química , Fluoretação/normas , Intoxicação por Flúor/etiologia , Intoxicação por Flúor/prevenção & controle , Fluoretos/metabolismo , Fluorose Dentária/etiologia , Fluorose Dentária/prevenção & controle , HumanosRESUMO
This study was conducted to measure the activity of the enzyme glutathione S-transferase (GST) in saliva and to compare the activity of this enzyme in children with and without dental fluorosis in communities with different concentrations of naturally fluoridated water. A total of 141 schoolchildren participated in this cross-sectional study. Children were selected from two communities: one with a low (0.4 ppm) and the other with a high (1.8 ppm) water fluoride concentration. Dental fluorosis was evaluated by applying the Thylstrup and Fejerskov Index (TFI) criteria. Stimulated saliva was obtained, and fluoride concentration and GST activity were measured. The GST activity was compared among children with different levels of dental fluorosis using multinomial logistic regression models and odds ratios (OR). The mean age of the children was 10.6 (±1.03) years. Approximately half of the children showed dental fluorosis (52.5 %). The average GST activity was 0.5678 (±0.1959) nmol/min/µg. A higher concentration of fluoride in the saliva was detected in children with a higher GST activity (p = 0.039). A multinomial logistic regression model used to evaluate the GST activity and the dental fluorosis score identified a strong association between TFI = 2-3 (OR = 15.44, p = 0.007) and TFI ≥ 4 (OR = 55.40, p = 0.026) and the GST activity level, compared with children showing TFI = 0-1, adjusted for age and sex. Schoolchildren with higher levels of dental fluorosis and a higher fluoride concentration in the saliva showed greater GST activity. The increased GST activity most likely was the result of the body's need to inactivate free radicals produced by exposure to fluoride.
Assuntos
Água Potável/química , Fluoretação , Fluoretos/metabolismo , Fluorose Dentária/diagnóstico , Glutationa Transferase/metabolismo , Western Blotting , Catalase/metabolismo , Criança , Estudos Transversais , Feminino , Fluorose Dentária/enzimologia , Humanos , Modelos Logísticos , Masculino , México , Análise Multivariada , Razão de Chances , Saliva/química , Saliva/enzimologia , Superóxido Dismutase-1/metabolismoRESUMO
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.
Assuntos
Fluoretos/toxicidade , Fluorose Dentária/genética , Predisposição Genética para Doença , Fígado/efeitos dos fármacos , Fígado/metabolismo , Proteínas/análise , Proteoma/efeitos dos fármacos , Animais , Fluoretos/análise , Fluoretos/metabolismo , Expressão Gênica , Masculino , Espectrometria de Massas/métodos , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos A , Estresse Oxidativo/efeitos dos fármacos , Domínios e Motivos de Interação entre Proteínas , Proteínas/efeitos dos fármacos , Proteínas/genética , Proteômica/métodos , Valores de Referência , Fatores de TempoRESUMO
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.