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POTENT ANTI-INFLAMMATORY ACTIVITY OF BETULINIC ACID TREATMENT IN A MODEL OF LETHAL ENDOTOXEMIA
Endotoxemia
Anti-inflammatory activity
Macrophages
Cytokines
Autor
Afiliación
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil
Federal University of Paraíba. Laboratory of Pharmaceutical Technology. João Pessoa, PB, Brasil
Federal University of Paraíba. Laboratory of Pharmaceutical Technology. João Pessoa, PB, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil / State University of Bahia. Department of Life Sciences. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil / São Rafael Hospital. Center of Biotecnology and Cell Therapy. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil / São Rafael Hospital. Center of Biotecnology and Cell Therapy. Salvador, BA, Brasil
Federal University of Paraíba. Laboratory of Pharmaceutical Technology. João Pessoa, PB, Brasil
Federal University of Paraíba. Laboratory of Pharmaceutical Technology. João Pessoa, PB, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil / State University of Bahia. Department of Life Sciences. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil / São Rafael Hospital. Center of Biotecnology and Cell Therapy. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil / São Rafael Hospital. Center of Biotecnology and Cell Therapy. Salvador, BA, Brasil
Resumen en ingles
Betulinic acid (BA) is a lupane-type triterpene with a number of biological activities already reported. While
potent anti-HIV and antitumoral activities were attributed to BA, it is considered to have a moderate antiinflammatory
activity. Here we evaluated the effects of BA in a mouse model of endotoxic shock. Endotoxemia
was induced through intraperitoneally LPS administration, nitric oxide (NO) and cytokines were assessed by
Griess method and ELISA, respectively. Treatment of BALB/c mice with BA at 67 mg/kg caused a 100% survival
against a lethal dose of lipopolysaccharide (LPS). BA treatment caused a reduction in TNF-α production induced
by LPS but did not alter IL-6 production. Moreover, BA treatment increased significantly the serumlevels of IL-10
compared to vehicle-treated, LPS-challenged mice. To investigate the role of IL-10 in BA-induced protection,
wild-type and IL-10−/− mice were studied. In contrast to the observations in IL-10+/+ mice, BA did not protect
IL-10−/− mice against a lethal LPS challenge. Addition of BA inhibited the production of pro-inflammatory
mediators by macrophages stimulated with LPS, while promoting a significant increase in IL-10 production.
BA-treated peritoneal exudate macrophages produced lower concentrations of TNF-α and NO and higher concentrations
of IL-10 upon LPS stimulation. Similarly, macrophages obtained from BA-treated mice produced
less pro-inflammatory mediators and increased IL-10 when compared to non-stimulated macrophages obtained
fromvehicle-treatedmice. In conclusion,we have shown that BA has a potent anti-inflammatory activity in vivo,
protecting mice against LPS by modulating TNF-α production by macrophages in vivo through a mechanism
dependent on IL-10.
Palabras clave en ingles
Betulinic acidEndotoxemia
Anti-inflammatory activity
Macrophages
Cytokines
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