Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/34117
Title: Betulinic Acid Derivative BA5, Attenuates Inflammation and Fibrosis in Experimental Chronic Chagas Disease Cardiomyopathy by Inducing IL-10 and M2 Polarization
Authors: Meira, Cássio Santana
Santos, Emanuelle de Souza
Santo, Renan Fernandes do Espírito
Vasconcelos, Juliana Fraga
Orge, Iasmim Diniz
Nonaka, Carolina Kymie Vasques
Barreto, Breno Cardim
Caria, Alex Cleber Improta
Silva, Daniela Nascimento
Barbosa Filho, José Maria
Macambira, Simone Garcia
Moreira, Diogo Rodrigo Magalhães
Soares, Milena Botelho Pereira
Affilliation: Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. Science and Health Institute. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Center for Biotechnology and Cell Therapy. Salvador, BA, Brazil.
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Center for Biotechnology and Cell Therapy. Salvador, BA, Brazil.
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Center for Biotechnology and Cell Therapy. Salvador, BA, Brazil.
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Center for Biotechnology and Cell Therapy. Salvador, BA, Brazil.
Hospital São Rafael. Center for Biotechnology and Cell Therapy. Salvador, BA, Brazil.
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Center for Biotechnology and Cell Therapy. Salvador, BA, Brazil.
Federal University of Paraíba. Laboratory of Pharmaceutical Technology. João Pessoa, Brasil.
Federal University of Bahia. Science and Health Institute. Salvador, BA, Brasil / Hospital São Rafael. Center for Biotechnology and Cell Therapy. Salvador, BA, Brazil.
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.
Abstract: Chronic Chagas disease cardiomyopathy (CCC) is a major cause of heart disease in Latin America and treatment for this condition is unsatisfactory. Here we investigated the effects of BA5, an amide semi-synthetic derivative betulinic acid, in a model of CCC. Mice chronically infected with T. cruzi were treated orally with BA5 (10 or 1 mg/Kg), three times per week, for 2 months. BA5 treatment decreased inflammation and fibrosis in heart sections but did not improve exercise capacity or ameliorate cardiac electric disturbances in infected mice. Serum concentrations of TNF-α, IFN-γ, and IL-1β, as well as cardiac gene expression of pro-inflammatory mediators, were reduced after BA5 treatment. In contrast, a significant increase in the anti-inflammatory cytokine IL-10 concentration was observed in BA5-treated mice in both tested doses compared to vehicle-treated mice. Moreover, polarization to anti-inflammatory/M2 macrophage phenotype was evidenced by a decrease in the expression of NOS2 and proinflammatory cytokines and the increase in M2 markers, such as Arg1 and CHI3 in mice treated with BA5. In conclusion, BA5 had a potent anti-inflammatory activity on a model of parasite-driven heart disease related to IL-10 production and a switch from M1 to M2 subset of macrophages.
Keywords: Trypanosoma cruzi
Betulinic acid derivative
Immunomodulation
Chagas disease
Cardiomyopathy
keywords: Trypanosoma cruzi
Derivado do ácido betulínico
Imunomodulação
Doença de chagas
Cardiomiopatia
Issue Date: 2019
Publisher: Frontiers Media
Citation: MEIRA, Cassio Santana et al. Betulinic Acid Derivative BA5, Attenuates Inflammation and Fibrosis in Experimental Chronic Chagas Disease Cardiomyopathy by Inducing IL-10 and M2 Polarization. Frontiers in Immunology, p. 1-9, June 2019.
DOI: 10.3389/fimmu.2019.01257
ISSN: 1664-3224
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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