Efeitos e mecanismos de ação da Tributirina na proteção da colite ulcerativa induzida por sulfato de sódio dextrano

Abstract

Tributyrin is the triacylglycerol composed by three molecules of butyric acid, which has beneficial effects in intestinal health due to its trophic, anti-inflammatory, pro-apoptotic and anti-carcinogenic effects. Our goal was to evaluate the efficacy and possible mechanisms of tributyrin supplementation in experimental colitis induced by dextran sodium sulfate. For that, mice received standard (control) or TBT-supplemented (0,5%) diets for ten or fifteen days. Colitis was induced by dextran sodium sulfate administration from the seventh experimental day, for three or seven days. Mucosa damage, percentage and activation of immune cells: eosinophil, neutrophil, macrophage, dendritic cell, B lymphocytes, helper T lymphocytes and regulatory T lymphocytes, and cytokine TNF-, INF-, IL-4, IL-17, IL-1, TGF- and IL-10 were determinated by histological score, flow cytometry and ELISA, respectively. Intravital microscopy assessed the in vivo leukocyte rolling and adhesion. Oxidative stress was determined by hydroperoxide concentration and superoxide dismutase and catalase activities. 99mTcDTPA (diethylenetriaminepentacetate acid) was used as marker of intestinal permeability. Compared to colitis group (non-supplemented), Colitis + TBT group presented reduced mucosal damage and neutrophil and eosinophil mucosa infiltrations associated with higher percentage of regulatory T cells and TGF- and IL-10 anti-inflammatory cytokines in the propria lamina. In vivo colon microvasculature leukocyte adhesion was decreased after tributyrin intake. Lower level of hydroperoxide and higher superoxide dismutase and catalase activities were associated with tributyrin supplementation. Colitis + TBT mice showed reduced intestinal permeability to levels between control and colitis groups. In addition, with three days intake dextran sodium sulfate, mucosal damage was observed equal in both groups with colitis induction, there was increased neutrophil infiltration, and increased oxidative stress by increasing the concentration of hydroperoxides and decreased activity catalase in these two groups, showing that tributyrin leads to improvement of the disease by modulation of oxidative stress and neutrophil infiltration. In conclusion, our results suggest that orally administered tributyrin has positive effects in experimental colitis, restructuring the colonic mucosa by modulating the immune response, increasing concentration of anti-inflammatory cytokines and regulatory T cell population and decreasing infiltration of eosinophils and neutrophils, and by modulating oxidative stress by increasing activity of antioxidant enzymes.