Efeito imunomodulador do Kanferol glicolisado em modelo de asma alérgica experimental

• Autor(a) principal: Medeiros, Karina Carla de Paula
• Data de Publicação: 2009
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UFPB
• Texto Completo: https://repositorio.ufpb.br/jspui/handle/tede/6846
• topic: Flavonóide; Kanferol glicosilado; Asma alérgica; Ovalbumina; Hiperreatividade brônquica; Flavonoid; Glycoside kampherol; Allergic asthma; Ovalbumin; Bronchial hyperreactivity; CIENCIAS BIOLOGICAS::FARMACOLOGIA

Asthma is a chronic inflammatory disease characterized by cell migration and bronchial hyperreactivity (HRB). One strategy to treat allergic diseases is the development of new drugs with good efficacy and few side effects. Flavonoids are plant compounds known for its antioxidant, antiallergic and anti-inflammatory activities. Based on this premise, the study aimed to select flavonoids by the immunopharmacological screening and to evaluate prophylactic and therapeutic treatments in the experimental asthma model. For this purpose the flavonoids tested were myricetin, isoramnetin and glycosylated kampherol known as 3-O-[β-D-glycopiranosil-(1→6)-α-L-rhamnopyranosyl]-7-O-α-L-rhamnopyranosyl-kamferol (GRRK). The experimental model was BALB/c mice sensitized and challenged with ovalbumin (OVA) and the treatments were before (prophylactic) or after (therapeutic) to establishment of the experimental asthma model. The three flavonoids inhibited the animal death during the anaphylactic chock reaction induced by OVA and the inflammatory cell migration to the lung; however only the GRRK was used in the following experiments because of its best yield in the purification process. Both prophylactic and therapeutic treatments with GRRK (30 mg/kg) decreased significantly the total number of inflammatory cells (P< 0.05), eosinophils cells (P< 0.05), IL-5 (P< 0.05) and IL-13 (P< 0.05) production from bronchoalveolar lavage (BAL), IgE OVA-specific title (P< 0.01) in the sera, the bronchial hyperreactivity (HRB) (P< 0.05) induced by methacholine and mucus production (P< 0.001) by the globbet cells from the lung as compared with non-treated GRRK animals. The results obtained in the different treatments with GRRK were statistically comparable with that observed in the OVA-sensitized group treated with dexametasone. Moreover, treatment with GRRK was able to reduce the number of CD4+ T cells (p <0.001), B cells (p <0.001), expression of major complex of compatibility II class (MHC II class) and CD40 molecules in the antigen presenting cells (CD11b+ CD11c+) from BAL. Although the GRRK induced a suppressive effect in the Th2 immune response it was not able to exacerbate the Th1 immune response by IFN- production. The production of this cytokine was not modified when compared with non treated animals. The GRRK treatment also was not able to modify the regulatory immune response because there was no significant change in the production of TGF- and the number of TCD4+Foxp3+, a marker of LT regulatory (TReg). These results demonstrated that GRRK treatment before (prophylactic) or after (therapeutic) the establishment of allergic asthma, restored the morpho-functional changes in the airways by Th2-dependent immunossupression, although independent of Th1 and TReg.