Extrato padronizado de própolis EPP-AR® aumenta a sobrevida em camundongos imunossuprimidos com sepse induzida por Candida albicans

Detalhes bibliográficos
Ano de defesa: 2017
Autor(a) principal: BRAGA, Thiare Silva Fortes lattes
Orientador(a): NASCIMENTO, Flávia Raquel Fernandes do
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal do Maranhão
Programa de Pós-Graduação: PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS DA SAÚDE/CCBS
Departamento: DEPARTAMENTO DE MEDICINA I/CCBS
País: Brasil
Palavras-chave em Português:
Palavras-chave em Inglês:
Área do conhecimento CNPq:
Link de acesso: http://tedebc.ufma.br:8080/jspui/handle/tede/1867
Resumo: Propolis produced by bees Apis mellifera is a resinous balsamic material used to protect the hive against fungi, bacteria, viruses and insects. Among the antimicrobial activities of propolis already proven, the antifungal action observed in strains of Candida albicans, commensal fungus of the oro-gastrointestinal tract and skin, associated with opportunistic infections, local or systemic, especially in immunosuppressed patients, are highlighted. The objective of this study was to evaluate the effect of treatment with standardized extract of propolis on systemic infection caused by C. albicans in immunosuppressed mice. Initially the C57Bl/ 6 mice were immunosuppressed with dexamethasone (3mg / kg) for one week and, on the eighth day, were infected intraperitoneally with C. albicans blastopores (2x106). After 24 hours of infection, the daily treatment of the animals with propolis at the doses of 10 and 100 mg/kg was initiated for 15 days intraperitoneally. Immunosuppression with dexamethasone was maintained for all the analysis. At the end of the 15 days, all the animals treated with propolis at the dose of 100 mg/kg were kept alive, while all the animals from the other groups had already died. From then on, it was possible to investigate possible immunological mechanisms to explain this effect. For this, the same protocol of immunosuppression and infection described above was repeated, however, the treatment was performed in a single application of propolis at a dose of 100 mg/kg, 24 hours after infection and the tests were performed 24 hours after this treatment. Treatment with propolis reduced the colony forming units in the peritoneum and spleen. In addition, propolis reversed dexamethasone-induced immunosuppression, increasing the number of circulating leukocytes, mainly neutrophils, proliferation of splenocytes, recruitment of leukocytes to the site of infection and increase of CD4+ T lymphocytes. Regarding the inflammatory mediators, it was observed that the treatment with propolis induced the increase of the ex vivo production of nitric oxide by peritoneal cells and the reduction of plasmatic inflammatory cytokines (IL-6 and TNF-α). Finally, in an in vitro experiment, peritoneal macrophages were treated with dexamethasone (4 μg/mL), for 48 hours, and then treated with propolis (100 μg/mL) for 12 hours. Then, cells were incubated with C. albicans for 1 hour. In this assay, it was observed that propolis increased phagocytosis, without, however, altering Dectin-1 and Mannose receptor expression. In conclusion, the standardized extract of propolis increased life expectancy and reduced C. albicans dissemination in immunosuppressed mice. Such effects are probably due to its ability to reverse dexamethasone-induced immunosuppression, recruit and activate effector immune cells to the site of infection, and reduce serum inflammatory cytokines, thereby reducing the progression of the deleterious aspects of systemic candidemia.