RESUMO
Liver fibrosis is a complex process characterized by the excessive accumulation of extracellular matrix (ECM) and an alteration in liver architecture, as a result of most types of chronic liver diseases such as cirrhosis, hepatocellular carcinoma (HCC) and liver failure. Maresin-1 (MaR1) is derivative of ω-3 docosahexaenoic acid (DHA), which has been shown to have pro-resolutive and anti-inflammatory effects. We tested the hypothesis that the application of MaR1 could prevent the development of fibrosis in an animal model of chronic hepatic damage. Sprague-Dawley rats were induced with liver fibrosis by injections of diethylnitrosamine (DEN) and treated with or without MaR1 for four weeks. In the MaR1-treated animals, levels of AST and ALT were normalized in comparison with DEN alone, the hepatic architecture was improved, and inflammation and necrotic areas were reduced. Cell proliferation, assessed by the mitotic activity index and the expression of Ki-67, was increased in the MaR1-treated group. MaR1 attenuated liver fibrosis and oxidative stress was induced by DEN. Plasma levels of the pro-inflammatory mediators TNF-α and IL-1ß were reduced in MaR1-treated animals, whereas the levels of IL-10, an anti-inflammatory cytokine, increased. Interestingly, MaR1 inhibited the translocation of the p65 subunit of NF-κB, while increasing the activation of Nrf2, a key regulator of the antioxidant response. Finally, MaR1 treatment reduced the levels of the pro-fibrotic mediator TGF-ß and its receptor, while normalizing the hepatic levels of IGF-1, a proliferative agent. Taken together, these results suggest that MaR1 improves the parameters of DEN-induced liver fibrosis, activating hepatocyte proliferation and decreasing oxidative stress and inflammation. These results open the possibility of MaR1 as a potential therapeutic agent in fibrosis and other liver pathologies.
Assuntos
Ácidos Docosa-Hexaenoicos/farmacologia , Inflamação/patologia , Cirrose Hepática/metabolismo , Cirrose Hepática/prevenção & controle , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo , Animais , Apoptose/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Citocinas/sangue , Dietilnitrosamina , Ácidos Docosa-Hexaenoicos/administração & dosagem , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Inflamação/sangue , Inflamação/complicações , Mediadores da Inflamação/sangue , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Fígado/efeitos dos fármacos , Fígado/lesões , Fígado/patologia , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Masculino , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Receptores Citoplasmáticos e Nucleares/metabolismoRESUMO
Mediante análisis descriptivo cualitativo, se caracterizaron cuatro variedades de té (Thea Sinensis): Té argentino Orange Pekoe (OP) (negro), Té Brasil OP (negro), Té Ceilán OP (negro) y Té Daarjeling OP (verde) La apariencia de las hojas secas de té se caracterizaron cualitativamente, comparándolas con hojas secas estándares. Se evaluó: color, forma y regularidad de las hojas, presencia de fibra y de estacas. Las diferencias obtenidas, se relacionaron con las diferencias producidas por efecto del proceso de fermentación del té. Los licores de té se caracterizaron en base a descriptores de sabor y aroma generados por un panel sensorial entrenado. El color y la astringencia se cuantificaron por medio de una escala lineal no estructurada, comparando con estándares calificados. Con el fin de relacionar el análisis sensorial y la composición química de las distintas variedades de té, se hicieron las determinaciones de humedad, materia seca, extracto acuoso, taninos y cafeína. Se definió el color en función de la materia seca, extracto acuoso y taninos y la astringencia en función del extracto acuoso, materia seca y humedad. El Análisis de Varianza de 3 factores: muestras, jueces, repeticiones señaló que se diferenciaron significativamente 4 grupos de té para astringencia y 3 para color, no existiendo diferencias significativas entre los jueces ni entre repeticiones. Se calcularon mediante análisis de regresión multifactorial, las ecuaciones de color y astringencia en función de las variables químicas determinadas