RESUMEN
OBJECTIVE: Ouabain, an inhibitor of Na+/K+-ATPase, is a type of endogenous hormone synthesized in the adrenal cortex and hypothalamus. Previous studies found that ouabain potently inhibited acute inflammatory reactions such as type 2 inflammation and regulated immunological processes. In this study, we aimed to investigate ouabain effect on allergic asthma. METHODS: BALB/c mice were submitted to chronic airway allergic inflammation induced by an ovalbumin (OVA) protocol. The animals were treated with ouabain or standard drug, budesonide. The following parameters were evaluated: cell migration, cytokine profile, IgE levels, lung histological modifications and MAPK activation. RESULTS: At first, it was observed that ouabain reduced OVA-induced cell migration into the lung, observed by bronchoalveolar lavage fluid (BALF) cell counting and lung histological analysis (HE stain). Additionally, ouabain negatively modulated alarmins (IL-33 and TSLP), Th2 high cytokines levels (IL-1ß and IL-4) and tissue remodeling markers such as TNF-α and TGF-ß. Treatment with ouabain also reduced OVA-specific IgE titers in BALF and serum, respectively, when compared to the OVA group. Lung histological parameters, including collagen deposition and mucus production induced by OVA were also attenuated by ouabain treatment. Finally, our results showed that p38 mitogen-activated protein kinase (MAPK) signaling pathways were suppressed by ouabain in this model. All these parameters were reduced by budesonide, a steroidal anti-inflammatory standard drug. CONCLUSION: These data together suggest that, in addition to its acute anti-inflammatory action, ouabain is also able to modulate allergic asthma.
Asunto(s)
Remodelación de las Vías Aéreas (Respiratorias) , Asma , Ouabaína , Animales , Antiinflamatorios/farmacología , Asma/inducido químicamente , Asma/tratamiento farmacológico , Líquido del Lavado Bronquioalveolar , Budesonida/farmacología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Inmunoglobulina E , Inflamación/tratamiento farmacológico , Pulmón/patología , Ratones , Ratones Endogámicos BALB C , Ouabaína/farmacología , OvalbúminaRESUMEN
Psoriasis is a chronic, inflammatory, immune-mediated disease affecting 1-3% of the population worldwide. This work seeks to draw a profile of patients with psoriasis, analyzing socioeconomic, anthropometric, and clinical aspects. For this, medical records from 81 individuals who received medical care in a university hospital in 2014 were consulted. It was observed that the patients were mostly dark-skinned black adult men, with a low education level and a low income, who were sedentary, former smokers, obese, with an increase in waist circumference, and who did not consume alcohol. Psoriasis vulgaris predominated, beginning mainly on the scalp, hands, and feet. In addition, many presented some type of associated comorbidity and had relatives with psoriasis.
Asunto(s)
Psoriasis/epidemiología , Adolescente , Adulto , Brasil/epidemiología , Niño , Preescolar , Comorbilidad , Femenino , Hospitales Universitarios/estadística & datos numéricos , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Conducta Sedentaria , Factores Socioeconómicos , Circunferencia de la Cintura , Adulto JovenRESUMEN
This study evaluated the effects of 2-amino-thiophene derivatives on the promastigote and amastigote forms of Leishmania (Leishmania) amazonensis and their possible mechanisms of action. Initially, we evaluated the antileishmanial activity of ten 2-amino-thiophene derivatives on promastigote and axenic amastigote forms of Leishmania amazonensis and their cytotoxicity against murine macrophages and human red blood cells. Three promising compounds were selected for studies of the cell death process using flow cytometry analysis and a DNA fragmentation assay. The effects of the compounds were assessed on intramacrophagic amastigotes, and the modulation of cytokine and NO production was investigated. All thiophene derivatives showed antileishmanial activity against promastigotes and axenic amastigotes with less toxicity for murine macrophages and human red blood cells. The best values were obtained for compounds containing a lateral indole ring. Docking studies suggested that these compounds played an important role in inhibiting trypanothione reductase (TryR) activity. The selected compounds SB-200, SB-44, and SB-83 induced apoptosis in promastigotes involving phosphatidylserine externalization and DNA fragmentation in a pattern similar to that observed for the positive control. Additionally, SB-200, SB-44, and SB-83 significantly reduced the infection index of macrophages by the parasites; for compounds SB-200 and SB-83 this reduction was associated with increased TNF-α, IL-12, and NO levels. This study demonstrated the effective and selective action of 2-amino-thiophene derivatives against L. amazonensis, resulting in apoptosis-like cell death and immunomodulation in vitro. The results suggest that they are promising compounds for the development of new leishmanicidal drugs.