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    Mecanismos envolvidos no efeito do tratamento com Deidrodieugenol em modelo de asma mista
    (Universidade Federal de São Paulo (UNIFESP), 2020-03-05) Silva, Rafael Cossi Da [UNIFESP]; Prado, Carla Maximo [UNIFESP]; Universidade Federal de São Paulo
    Asthma is a disease characterized by bronchial inflammation and it still a public health problem even with the existence of a standard treatment consisting of corticosteroids and bronchodilators. Previously, our laboratory studies had shown that dehydrodieugenol, a dimer of the anti-inflammatory eugenol molecules, appears to be promising in reducing the neutrophil inflammatory response, with less toxicity than eugenol. Objectives. The present project aims to understand mechanisms involved in this model of mixed asthma and to test if the treatment with dehydrodieugenol will be effective in reducing inflammation. Materials and methods. Balb/c male mice, aged from 6 to 8 weeks, underwent to 24-day sensitization protocol, with ovalbumin and Freud's Adjuvant, for induction of mixed asthma. The dehydrodieugenol treatment were administered in the last four days, and the animals were euthanized on the last day of treatment. It was used animals sensitized with ovalbumin associated with Freud's adjuvant lungs, where essential cytokines in the pathophysiology of mixed asthma were evaluated, such as IL-1β, IL-8, IL-13, IL-4, IL-17, INF-γ, CXCL9 , CD68, TGF-β and IL-6; in addition to assessing the MAPK pathway in the lung. Finally, in histological sections, the pulmonary remodeling process was evaluated. Results. Compared to the ovoalbumin group, 10mg/kg dehydrodieugenol group decreased the levels of total cells (P <0.001), neutrophils (P <0.05), eosinophil (P <0.01), macrophages (P <0.01), lymphocytes (P <0.05), ERK1/2 phosphorylation (P <0.01), IL-1β cytokine levels (P <0.01), messenger RNA levels (P <0.05) and cytokines (P <0.01) of KC, levels of IL-6 messenger RNA (P <0.05), levels of INF-γ (P <0.01), levels of IL-13 cytokine (P <0.01), the levels of IL-4 messenger RNA (P <0.05), and a decrease in bronchoconstriction (P <0.001), smooth muscle thickness (P <0.01) and collagen deposition (P <0.05) in the airway. Conclusion. The results showed that the 10mg/kg dehydrodieugenol group decreased the inflammation more than 20mg/kg group. In addition, it was possible to perceive that in mixed asthma the most common inflammatory response is via Th1, justifying the resistance to standard treatment described in literature. Dehydrodieugenol has been shown to be efficient both in the inflammatory response and in the improvement of pulmonary remodeling, being an interesting molecule to be studied as an alternative treatment for patient diagnosed with mixed asthma.