RESUMEN
Cardiomyopathy related to the absence of dystrophin is an important feature in Duchenne muscular dystrophy (DMD) and in the mdx mouse. Doxycycline (DOX) could be a potential therapy for mdx skeletal muscles dystrophy. We investigated whether the corticoid deflazacort (DFZ) plus DOX could improve cardiac mdx dystrophy better than DFZ alone, later (17 months) in dystrophy. Mdx mice (8 months old) received DFZ/DOX or DFZ for 9 months. The combined therapy was greater than DFZ in reducing fibrosis (60% decrease with DFZ/DOX and 40% with DFZ alone) in the right ventricle and transforming growth factor ß levels (6.8 ± 3.2 in untreated mdx mice, 2.8 ± 1.4 in combined therapy, and 4.6 ± 1.7 in DFZ; P < .05). Combined therapy more effectively ameliorated cardiac dysfunction (electrocardiogram [ECG]) than DFZ. Improvements were seen in the cardiomyopathy index (0.8 ± 0.1 in combined therapy and 1.0 ± 0.2 in DFZ), heart rate (418 ± 46 bpm in combined therapy and 457 ± 29 bpm in DFZ), QRS interval (11.3 ± 2 in combined therapy and 13.6 ± 1 in DFZ), and Q wave amplitude (-40.7 ± 21 in combined therapy and -90.9 ± 36 in DFZ). Both therapies decreased markers of inflammation (tumor necrosis factor α, nuclear factor κB, and metalloproteinase 9). DFZ/DOX improved mdx cardiomyopathy at this stage of the disease, supporting further clinical investigations.
Asunto(s)
Cardiomiopatías/tratamiento farmacológico , Doxiciclina/administración & dosificación , Distrofina/deficiencia , Distrofia Muscular de Duchenne/complicaciones , Pregnenodionas/uso terapéutico , Animales , Cardiomiopatías/etiología , Doxiciclina/toxicidad , Quimioterapia Combinada , Electrocardiografía , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Pregnenodionas/administración & dosificación , Pregnenodionas/toxicidadRESUMEN
This study aims at determining the Minimum Inhibitory Concentration with Escherichia coli ATCC 25922 and cytotoxicity to L929 cells (ATCC CCL-1) of the waste generated by doxycycline degradation by the Fenton process. This process has shown promise in this treatment thanks mainly to the fact that the waste did not show any relevant inhibitory effect on the test organism and no cytotoxicity to L-929 cells, thus demonstrating that the antibiotic properties were inactivated.
Asunto(s)
Antibacterianos/química , Doxiciclina/química , Peróxido de Hidrógeno/química , Hierro/química , Contaminantes Químicos del Agua/química , Animales , Antibacterianos/toxicidad , Línea Celular , Supervivencia Celular/efectos de los fármacos , Doxiciclina/toxicidad , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Fibroblastos/efectos de los fármacos , Humanos , Ratones , Pruebas de Sensibilidad Microbiana , Eliminación de Residuos Líquidos , Contaminantes Químicos del Agua/toxicidadRESUMEN
This article presents details of fabrication, biological activity (i.e., anti-matrix metalloproteinase [anti-MMP] inhibition), cytocompatibility, and bonding characteristics to dentin of a unique doxycycline (DOX)-encapsulated halloysite nanotube (HNT)-modified adhesive. We tested the hypothesis that the release of DOX from the DOX-encapsulated nanotube-modified adhesive can effectively inhibit MMP activity. We incorporated nanotubes, encapsulated or not with DOX, into the adhesive resin of a commercially available bonding system (Scotchbond Multi-Purpose [SBMP]). The following groups were tested: unmodified SBMP (control), SBMP with nanotubes (HNT), and DOX-encapsulated nanotube-modified adhesive (HNT+DOX). Changes in degree of conversion (DC) and microtensile bond strength were evaluated. Cytotoxicity was examined on human dental pulp stem cells (hDPSCs). To prove the successful encapsulation of DOX within the adhesives-but, more important, to support the hypothesis that the HNT+DOX adhesive would release DOX at subantimicrobial levels-we tested the antimicrobial activity of synthesized adhesives and the DOX-containing eluates against Streptococcus mutans through agar diffusion assays. Anti-MMP properties were assessed via ß-casein cleavage assays. Increasing curing times (10, 20, 40 sec) led to increased DC values. There were no statistically significant differences (p > .05) in DC within each increasing curing time between the modified adhesives compared to SBMP. No statistically significant differences in microtensile bond strength were noted. None of the adhesives eluates were cytotoxic to the human dental pulp stem cells. A significant growth inhibition of S. mutans by direct contact illustrates successful encapsulation of DOX into the experimental adhesive. More important, DOX-containing eluates promoted inhibition of MMP-1 activity when compared to the control. Collectively, our findings provide a solid background for further testing of encapsulated MMP inhibitors into the synthesis of therapeutic adhesives that may enhance the longevity of hybrid layers and the overall clinical performance of adhesively bonded resin composite restorations.
Asunto(s)
Antibacterianos/química , Recubrimientos Dentinarios/química , Doxiciclina/química , Nanotubos/química , Silicatos de Aluminio/síntesis química , Silicatos de Aluminio/química , Silicatos de Aluminio/toxicidad , Antibacterianos/síntesis química , Antibacterianos/toxicidad , Caseínas/efectos de los fármacos , Técnicas de Cultivo de Célula , Arcilla , Recubrimiento Dental Adhesivo , Pulpa Dental/citología , Pulpa Dental/efectos de los fármacos , Dentina/efectos de los fármacos , Dentina/ultraestructura , Recubrimientos Dentinarios/síntesis química , Recubrimientos Dentinarios/toxicidad , Doxiciclina/síntesis química , Doxiciclina/toxicidad , Humanos , Ensayo de Materiales , Metaloproteinasa 1 de la Matriz/efectos de los fármacos , Inhibidores de la Metaloproteinasa de la Matriz/química , Nanotubos/toxicidad , Polimerizacion , Cementos de Resina/síntesis química , Cementos de Resina/química , Cementos de Resina/toxicidad , Células Madre/efectos de los fármacos , Streptococcus mutans/efectos de los fármacos , Estrés Mecánico , Resistencia a la Tracción , Factores de TiempoRESUMEN
The aim of the present study was to evaluate the capacity of some root canal irrigants to induce genetic damage and/or cellular death in vitro. Murine fibroblast cells were exposed to ethylenediaminetetraacetic acid (EDTA), sodium hypochlorite (NaOCl), MTAD and citric acid in increasing concentrations for 3 h at 37ºC. The negative control group was treated with vehicle control (phosphate buffer solution - PBS) for 3 h at 37°C, and the positive control group was treated with methylmetanesulfonate, 1 μM. for 3 h at 37°C. Cytotoxicity was assessed by the trypan blue test and genotoxicity was evaluated by the single cell gel (comet) assay. The results showed that exposure to 2.5% and 5% NaOCl and 8.5% citric acid resulted in a significant cytotoxic effect. NaOCl, EDTA and citric acid did not produce genotoxic effects with respect to the comet assay data for all evaluated concentrations. Although MTAD was not a cytotoxic agent, it showed significant genotoxic effects at all tested concentrations (ANOVA and Tukey's test; p<0.05). NaOCl, EDTA and citric acid were found to be cytotoxic in a dose-dependent manner, but they were not genotoxic. MTAD did not cause cell death, but presented genotoxic effects.
O objetivo do presente estudo foi avaliar a capacidade de alguns irrigantes endodônticos em induzir danos genéticos e/ou morte celular in vitro. Células de fibroblastos murinos foram expostas ao ácido etilenodiaminotetracético (EDTA), hipoclorito de sódio (NaOCl), MTAD e ácido cítrico em concentrações crescentes durante 3 h a 37°C. O grupo controle negativo foi tratado com solução tampão fosfato - PBS por 3 h a 37° C e o grupo controle positivo foi tratado com metilmetanesulfonato a 1 μM por 3 h a 37° C. A citotoxicidade foi testada pelo azul de tripan e a genotoxicidade foi avaliada pelo teste do cometa. Os resultados apontaram que a exposição ao NaOCl a 2,5% e 5%, e ácido cítrico a 21% resultou em efeitos citotóxicos significativos. O NaOCl, EDTA e o ácido cítrico não produziram efeitos genotóxicos no que diz respeito aos dados obtidos pelo ensaio do Cometa em todas as concentrações testadas. Embora o MTAD não tenha sido um agente citotóxico, mostrou efeitos genotóxicos significativos em todas as concentrações testadas (ANOVA e teste de Tuckey; p<0,05). O NaOCl, o EDTA e o ácido cítrico mostraram-se citotóxicos de maneira dose-dependente, mas não genotóxicos. Por outro lado, apesar do MTAD não ter causado a morte celular, foi genotóxico em todas as concentrações testadas.
Asunto(s)
Animales , Ratones , Muerte Celular/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Dentina/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Mutágenos , Irrigantes del Conducto Radicular/toxicidad , Análisis de Varianza , Línea Celular , Ensayo Cometa , Ácido Cítrico/toxicidad , Doxiciclina/toxicidad , Ácido Edético/toxicidad , Fibroblastos/citología , Polisorbatos/toxicidad , Hipoclorito de Sodio/toxicidad , Azul de Tripano/químicaRESUMEN
The aim of the present study was to evaluate the capacity of some root canal irrigants to induce genetic damage and/or cellular death in vitro. Murine fibroblast cells were exposed to ethylenediaminetetraacetic acid (EDTA), sodium hypochlorite (NaOCl), MTAD™ and citric acid in increasing concentrations for 3 h at 37ºC. The negative control group was treated with vehicle control (phosphate buffer solution - PBS) for 3 h at 37°C, and the positive control group was treated with methylmetanesulfonate, 1 µM. for 3 h at 37°C. Cytotoxicity was assessed by the trypan blue test and genotoxicity was evaluated by the single cell gel (comet) assay. The results showed that exposure to 2.5% and 5% NaOCl and 8.5% citric acid resulted in a significant cytotoxic effect. NaOCl, EDTA and citric acid did not produce genotoxic effects with respect to the comet assay data for all evaluated concentrations. Although MTAD was not a cytotoxic agent, it showed significant genotoxic effects at all tested concentrations (ANOVA and Tukey's test; p<0.05). NaOCl, EDTA and citric acid were found to be cytotoxic in a dose-dependent manner, but they were not genotoxic. MTAD did not cause cell death, but presented genotoxic effects.