RESUMEN
Triclosan (TCS) is a chlorinated diphenyl ether and a possible active agent against microorganisms. Due to its probability of reducing dental plaque accumulation, TCS can be added as a substance for oral hygiene. Aim: To evaluate the efficacy and antimicrobial capacity of TCS against Pseudomonas aeruginosa and Streptococcus mutans. Methods: This work evaluates the percentage of bacteria inhibition of P. aeruginosa (ATCC 27853) and S. mutans (ATCC 25175). TCS concentrations between 2 and 128 µg.mL-1 were tested. Results: An inhibitory potential of TCS was found against S. mutans. No percentage of inhibition was detected against P. aeruginosa (technical and biological triplicate). Conclusion: TCS, an antimicrobial agent used in dentifrices, can reduce S. mutans levels therefore these dentifrices should be indicated for patients with a high risk of caries. However, further study is needed, including antimicrobial analyses against other microbial conditions
Asunto(s)
Pseudomonas aeruginosa , Streptococcus mutans , Triclosán/antagonistas & inhibidores , Caries Dental , Productos para la Higiene Dental y Bucal , Antiinfecciosos Locales , Enfermedades de la BocaRESUMEN
Emerging research supports that triclosan (TCS), an antimicrobial agent found in thousands of consumer products, exacerbates colitis and colitis-associated colorectal tumorigenesis in animal models. While the intestinal toxicities of TCS require the presence of gut microbiota, the molecular mechanisms involved have not been defined. Here we show that intestinal commensal microbes mediate metabolic activation of TCS in the colon and drive its gut toxicology. Using a range of in vitro, ex vivo, and in vivo approaches, we identify specific microbial ß-glucuronidase (GUS) enzymes involved and pinpoint molecular motifs required to metabolically activate TCS in the gut. Finally, we show that targeted inhibition of bacterial GUS enzymes abolishes the colitis-promoting effects of TCS, supporting an essential role of specific microbial proteins in TCS toxicity. Together, our results define a mechanism by which intestinal microbes contribute to the metabolic activation and gut toxicity of TCS, and highlight the importance of considering the contributions of the gut microbiota in evaluating the toxic potential of environmental chemicals.
Asunto(s)
Proteínas Bacterianas/antagonistas & inhibidores , Carcinógenos/antagonistas & inhibidores , Colitis/prevención & control , Neoplasias Colorrectales/prevención & control , Glucuronidasa/antagonistas & inhibidores , Inhibidores de Glicósido Hidrolasas/farmacología , Triclosán/antagonistas & inhibidores , Animales , Antiinfecciosos Locales/química , Antiinfecciosos Locales/metabolismo , Antiinfecciosos Locales/toxicidad , Anticarcinógenos/química , Anticarcinógenos/farmacología , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Sitios de Unión , Biotransformación , Carcinogénesis/efectos de los fármacos , Carcinogénesis/metabolismo , Carcinógenos/química , Carcinógenos/metabolismo , Carcinógenos/toxicidad , Colitis/inducido químicamente , Colitis/enzimología , Colitis/microbiología , Colon/efectos de los fármacos , Colon/microbiología , Colon/patología , Neoplasias Colorrectales/inducido químicamente , Neoplasias Colorrectales/enzimología , Neoplasias Colorrectales/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Expresión Génica , Glucuronidasa/química , Glucuronidasa/genética , Glucuronidasa/metabolismo , Inhibidores de Glicósido Hidrolasas/química , Humanos , Ratones , Ratones Endogámicos C57BL , Modelos Moleculares , Unión Proteica , Conformación Proteica en Hélice alfa , Conformación Proteica en Lámina beta , Dominios y Motivos de Interacción de Proteínas , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Triclosán/química , Triclosán/metabolismo , Triclosán/toxicidadRESUMEN
Triclosan (TCS), an antibacterial, has been shown to be an endocrine disruptor in the rat. We reported previously that TCS potentiated the estrogenic effect of ethinyl estradiol (EE) on uterine growth in rats exposed to EE and TCS in the uterotrophic assay, whereas TCS alone had no effect. To further characterize this potentiation, we evaluated the effect of co-exposure with lower doses of EE that are comparable to the concentrations in hormone replacement regimens and began to assess the mechanisms by which this potentiation occurs. Changes in uterine weight, epithelial cell growth, and estrogen-sensitive gene expression were assessed. TCS expectedly enhanced the uterotrophic response to EE, however at significantly lower doses of EE. Similarly, TCS increased the EE-induced stimulation of epithelial cell height following cotreatment. Cotreatment also enhanced the estrogen-induced change in gene expression, which was reversed with an ER antagonist. Furthermore, the TCS-induced potentiation was independent of ER activation, as no effects were observed in the ER TA assay.
Asunto(s)
Disruptores Endocrinos/toxicidad , Estrógenos/agonistas , Etinilestradiol/agonistas , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Lesiones Precancerosas/inducido químicamente , Triclosán/toxicidad , Útero/efectos de los fármacos , Animales , Antibacterianos/administración & dosificación , Antibacterianos/antagonistas & inhibidores , Antibacterianos/toxicidad , Forma de la Célula/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Disruptores Endocrinos/administración & dosificación , Disruptores Endocrinos/química , Antagonistas de Estrógenos/farmacología , Antagonistas de Estrógenos/uso terapéutico , Terapia de Reemplazo de Estrógeno/efectos adversos , Estrógenos/administración & dosificación , Estrógenos/efectos adversos , Estrógenos/farmacología , Etinilestradiol/efectos adversos , Etinilestradiol/antagonistas & inhibidores , Etinilestradiol/farmacología , Femenino , Tamaño de los Órganos/efectos de los fármacos , Lesiones Precancerosas/metabolismo , Lesiones Precancerosas/patología , Lesiones Precancerosas/prevención & control , Distribución Aleatoria , Ratas , Receptores de Estrógenos/agonistas , Receptores de Estrógenos/antagonistas & inhibidores , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismo , Triclosán/administración & dosificación , Triclosán/antagonistas & inhibidores , Útero/crecimiento & desarrollo , Útero/metabolismo , Útero/patología , DesteteRESUMEN
The objective of this study was to investigate the application of established D-value calculations to survival curves for various bacteria using the following antimicrobials: acidified sodium chlorite, triclosan, octanoic acid, and sodium hydroxide. D-values can be calculated in 3 ways, a linear regression, an endpoint calculation, or an average of multiple endpoint calculations. The assumption made in calculating a D-value is that the rate of kill follows 1st-order kinetics under specified treatment conditions. Each antimicrobial solution was challenged with approximately 108 CFU/mL of Staphylococcus aureus, Listeria monocytogenes, Salmonella enterica subsp. enterica, and Escherichia coli independently and in triplicate. Test systems were sampled at each of the 10 time points over a period of 7 min, neutralized, pour plated then incubated at 35 °C for 48 h (AOAC official method 960.09). Survival curves using the log-transformed data were calculated using regression analysis. Correlations coefficients for all linear regression analyses ranged between 0.291 and 0.982, with 6 of the 16 different treatment systems having an R2 value below 0.7. Methods used for calculating D-values should lead to the same result if the survival curve in a given condition is linear. The calculated D-values were different using endpoint analysis (Stumbo method), linear regression, and average of multiple endpoints. This study demonstrates the nonlinearity of inactivation curves of antimicrobials. D-value estimations cannot be reliably used to illustrate biocidal activity in antimicrobial test systems.
Asunto(s)
Antibacterianos/farmacología , Desinfectantes/farmacología , Algoritmos , Antibacterianos/antagonistas & inhibidores , Caprilatos/antagonistas & inhibidores , Caprilatos/farmacología , Cloruros/antagonistas & inhibidores , Cloruros/farmacología , Recuento de Colonia Microbiana , Desinfectantes/antagonistas & inhibidores , Escherichia coli/efectos de los fármacos , Cinética , Listeria monocytogenes/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana/efectos de los fármacos , Concentración Osmolar , Salmonella enterica/efectos de los fármacos , Hipoclorito de Sodio/antagonistas & inhibidores , Hipoclorito de Sodio/farmacología , Staphylococcus aureus/efectos de los fármacos , Estadística como Asunto , Tiosulfatos/química , Triclosán/antagonistas & inhibidores , Triclosán/farmacologíaRESUMEN
The anti-inflammatory properties of triclosan have been revealed in several recent studies, including an effect on histamine-induced inflammation. In other studies, the nature of the solvent has been shown to be of importance for the plaque inhibiting as well as the antibacterial potential of triclosan. This study was aimed at examining whether the nature of the solvent also may influence the anti-inflammatory capacity of triclosan and further to study a possible dose/ response relationship. The study was performed as 3 separate, double-blind experiments, comprising 10, 11 and 12 healthy females. In all 3 experiments, 5 sites on the lower part of the back of the volunteers were intradermally exposed to one drop of 1% histamine dihydrochloride for 15 min. The size of the resulting wheals was recorded before and after 40 min of triclosan treatment. In experiment 1, 4 different concentrations of triclosan in 2-fold dilutions in absolute alcohol (0.125%-1%) were applied on the histamine-induced wheals. In experiments 2 and 3, 4 different solutions containing 0.5% triclosan and a saline solution as negative control were used. The solvents in experiment 2 were as follows: (1) absolute alcohol (positive control), (2) propylene glycol (PG), (3) polyethylene glycol (PEG), (4) olive oil, and in experiment 3: (1) absolute alcohol (positive control), (2) Tween 80, (3) sodium carbonate, (4) soy oil. The results showed a dose/ response effect of triclosan and further that the solvent may be of importance for its anti-inflammatory potential.