RESUMEN
Indigo is a bis-indolic alkaloid that has antioxidant and anti-inflammatory effects reported in literature and is a promissory compound for treating chronic inflammatory diseases. This fact prompted to investigate the effects of this alkaloid in the experimental model of Duchenne muscular dystrophy. The main aim of this study was to evaluate the potential role of the indigo on oxidative stress and related signaling pathways in primary skeletal muscle cell cultures and in the diaphragm muscle from mdx mice. The MTT and Neutral Red assays showed no indigo dose-dependent toxicities in mdx muscle cells at concentrations analyzed (3.12, 6.25, 12.50, and 25.00 µg/mL). Antioxidant effect of indigo, in mdx muscle cells and diaphragm muscle, was demonstrated by reduction in 4-HNE content, H2O2 levels, DHE reaction, and lipofuscin granules. A significant decrease in the inflammatory process was identified by a reduction on TNF and NF-κB levels, on inflammatory area, and on macrophage infiltration in the dystrophic sample, after indigo treatment. Upregulation of PGC-1α and SIRT1 in dystrophic muscle cells treated with indigo was also observed. These results suggest the potential of indigo as a therapeutic agent for muscular dystrophy, through their action anti-inflammatory, antioxidant, and modulator of SIRT1/PGC-1α pathway.
Asunto(s)
Distrofia Muscular de Duchenne , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antioxidantes/metabolismo , Modelos Animales de Enfermedad , Peróxido de Hidrógeno/metabolismo , Carmin de Índigo/metabolismo , Carmin de Índigo/farmacología , Carmin de Índigo/uso terapéutico , Alcaloides Indólicos/metabolismo , Alcaloides Indólicos/farmacología , Alcaloides Indólicos/uso terapéutico , Ratones , Ratones Endogámicos mdx , Modelos Teóricos , Músculo Esquelético/metabolismo , Distrofia Muscular de Duchenne/tratamiento farmacológico , Transducción de Señal , Sirtuina 1/metabolismoRESUMEN
The effect of indigo dye effluent on the freshwater microalga Scenedesmus quadricauda ABU12 was investigated under controlled laboratory conditions. The microalga was exposed to different concentrations of the effluent obtained by diluting the dye effluent from 100 to 175 times in bold basal medium (BBM). The growth rate of the microalga decreased as indigo dye effluent concentration increased (p <0.05). The EC50 was found to be 166 dilution factor of the effluent. Chlorophyll a, cell density and dry weight production as biomarkers were negatively affected by high indigo dye effluent concentration, their levels were higher at low effluent concentrations (p <0.05). Changes in coenobia size significantly correlated with the dye effluent concentration. A shift from large to small coenobia with increasing indigo dye effluent concentration was obtained. We conclude that even at low concentrations; effluents from textile industrial processes that use indigo dye are capable of significantly reducing the growth and biomass production, in addition to altering the morphological characteristics of the freshwater microalga S. quadricauda. The systematic reduction in the number of cells per coenobium observed in this study further confirms that environmental stress affects coenobium structure in the genus Scenedesmus, which means it can be considered an important biomarker for toxicity testing.