RESUMEN
The effect of chronic fluoride (F) exposure from the drinking water on parameters related to glucose homeostasis was investigated. Wistar rats were randomly distributed into 2 groups (diabetic [D] and nondiabetic [ND]; n = 54 each). In D, diabetes was induced with streptozotocin. Each group was further divided into 3 subgroups (0, 10, or 50 mgF/L in drinking water). After 22 days of treatment, plasma and liver samples were collected. No alterations in glycemia, insulinemia, K(ITT), and HOMA2-IR (homeostasis model assessment 2 of insulin resistance) were seen for ND. F-exposure of D rats led to significantly lower insulinemia, without alterations in glycemia (increased %S). Proteomic analysis detected 19, 39, and 16 proteins differentially expressed for the comparisons D0 vs. D10, D0 vs. D50, and D10 vs. D50, respectively. Gene Ontology with the most significant terms in the comparisons D0 vs. D10, D0 vs. D50, and D50 vs. D10 were organic acid metabolic process and carboxylic acid metabolic process, organic acid metabolic process, and cellular ketone metabolic process. Analysis of subnetworks revealed that proteins with fold changes interacted with GLUT4 in comparison D0 vs. D10. Among these proteins, ERj3p was present in D10. Upregulation of this protein in the presence of F might help to explain the higher %S found in these animals. These data suggest that fluoride might enhance glucose homeostasis in diabetes and identify specific biological mechanisms that merit future studies.
Asunto(s)
Diabetes Mellitus Experimental/metabolismo , Fluoruros/administración & dosificación , Glucosa/metabolismo , Hipoglucemiantes/administración & dosificación , Resistencia a la Insulina , Animales , Glucemia/análisis , Ácidos Carboxílicos/metabolismo , Relación Dosis-Respuesta a Droga , Fluoruros/análisis , Ontología de Genes , Transportador de Glucosa de Tipo 4/metabolismo , Proteínas del Choque Térmico HSP40/metabolismo , Homeostasis/fisiología , Hipoglucemiantes/análisis , Insulina/sangre , Cetonas/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Pliegue de Proteína , Proteoma/análisis , Distribución Aleatoria , Ratas , Ratas Wistar , Estreptozocina , Abastecimiento de AguaRESUMEN
OBJECTIVE: Test the ability of acidic fluoridated solutions to enhance fluoride (F) bound on bacteria (1) and the effect of dentifrice consistency on plaque fluid F uptake (2). METHODS: (1) Streptococcus mutans isolates were grown in BHI medium (37°C/18h). Bacteria were washed either with EDTA or CaCl2 both at 1mM to remove or add calcium, respectively. Pellets were incubated with 12 mM NaF at pH 4.5 or 7 for 1 min and F was quantified in the lysates and supernatants with the electrode, after HMDS-facilitated diffusion. (2) A randomized, double-blind, crossover clinical trial was performed in three phases with nineteen adults (20-35 years) that used one of the dentifrices: commercial toothpaste (1100 ppm F, pH7.0 and conventional viscosity (Sorriso Fresh(®))); experimental liquid dentifrice (ELD) (1100 ppm F, pH7.0 and low viscosity [1.1% carboxymethylcellulose (CMC)]) and ELD (1100 ppm F and high viscosity pH7.0 (2.2% CMC)). F concentration in plaque fluid was analyzed using an inverted F electrode. RESULTS: (1) Significantly higher F amounts were detected in the lysates of bacteria incubated with NaF solution at pH4.5 compared to the supernatant, which was not seen at pH7.0, being this effect calcium-dependent. (2) Significantly higher F concentrations in plaque fluid were found 1h after toothbrushing compared to 12h, but no significant differences were seen among the toothpastes. CONCLUSIONS: F at low pH binds more efficiently to S. mutans than at neutral pH and dentifrice viscosity does not interfere in plaque fluid fluoride incorporation. CLINICAL SIGNIFICANCE: pH of the dentifrice but not consistency may be important to F uptake in plaque.
Asunto(s)
Placa Dental/tratamiento farmacológico , Dentífricos/química , Fluoruros/uso terapéutico , Adulto , Fluoruros/análisis , Fluoruros/farmacología , Humanos , Concentración de Iones de Hidrógeno , Streptococcus mutans/efectos de los fármacos , Streptococcus mutans/aislamiento & purificaciónRESUMEN
Prostaglandins (PGs) and leukotrienes (LTs) are produced in Mycobacterium tuberculosis (Mtb)-infected lungs and have immune suppressive and protective effects, respectively. Considering that both of these mediators are produced during mycobacterial infection, we investigated the specific and relative biological importance of each in regulating host response in experimental tuberculosis. Administration of celecoxib, which was found to reduce lung levels of PGE(2) and increase LTB(4), enhanced the 60-day survival of Mtb-infected mice in 14%. However administration of MK-886, which reduced levels of LTB(4) but did not enhance PGE(2), reduced 60-day survival from 86% to 43% in Mtb-infected mice, and increased lung bacterial burden. MK-886 plus celecoxib reduced survival to a lesser extent than MK-886 alone. MK-886- and MK-886 plus celecoxib-treated animals exhibited reduced levels of the protective interleukin-12 and gamma-interferon. Our findings indicate that in this model, the protective effect of LTs dominates over the suppressive effect of PGs.