| Author | Vasconcelos, Juliana Fraga | |
| Author | Meira, Cássio Santana | |
| Author | Silva, Daniela Nascimento | |
| Author | Nonaka, Carolina Kymie Vasques | |
| Author | Daltro, Pâmela Santana | |
| Author | Macambira, Simone Garcia | |
| Author | Domizi, Pablo Daniel | |
| Author | Borges, Valéria Matos | |
| Author | Santos, Ricardo Ribeiro dos | |
| Author | Souza, Bruno Solano de Freitas | |
| Author | Soares, Milena Botelho Pereira | |
| Access date | 2017-08-16T17:37:49Z | |
| Available date | 2017-08-16T17:37:49Z | |
| Document date | 2017 | |
| Citation | VASCONCELOS, J. F. et al. Therapeutic effects of sphingosine kinase inhibitor N,N-dimethylsphingosine (DMS) in experimental chronic Chagas disease cardiomyopathy. Scientific Reports, v.7, n. 1, p.6171, 2017. | pt_BR |
| ISSN | 2045-2322 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/20646 | |
| Sponsorship | National Council for Scientific and Technological Development (CNPq) and Bahia Research Foundation (FAPESB). | pt_BR |
| Language | eng | pt_BR |
| Publisher | Nature Publishing Group | pt_BR |
| Rights | open access | pt_BR |
| Subject in Portuguese | Cardiomiopatia chagásica | pt_BR |
| Subject in Portuguese | Doença de Chagas | pt_BR |
| Subject in Portuguese | Doença inflamatória | pt_BR |
| Subject in Portuguese | Trypanosoma cruzi | pt_BR |
| Subject in Portuguese | Tratamento | pt_BR |
| Subject in Portuguese | Ratos | pt_BR |
| Title | Therapeutic effects of sphingosine kinase inhibitor N,N-dimethylsphingosine (DMS) in experimental chronic Chagas disease cardiomyopathy | pt_BR |
| Type | Article | pt_BR |
| DOI | 10.1038/s41598-017-06275-z | |
| Abstract | Chagas disease cardiomyopathy is a parasite-driven inflammatory disease to which there are no effective treatments. Here we evaluated the therapeutic potential of N,N-dimethylsphingosine(DMS), which blocks the production of sphingosine-1-phosphate(S1P), a mediator of cellular events during inflammatory responses, in a model of chronic Chagas disease cardiomyopathy. DMS-treated, Trypanosoma cruzi-infected mice had a marked reduction of cardiac inflammation, fibrosis and galectin-3 expression when compared to controls. Serum concentrations of galectin-3, IFNγ and TNFα, as well as cardiac gene expression of inflammatory mediators were reduced after DMS treatment. The gene expression of M1 marker, iNOS, was decreased, while the M2 marker, arginase1, was increased. DMS-treated mice showed an improvement in exercise capacity. Moreover, DMS caused a reduction in parasite load in vivo. DMS inhibited the activation of lymphocytes, and reduced cytokines and NO production in activated macrophage cultures in vitro, while increasing IL-1β production. Analysis by qRT-PCR array showed that DMS treatment modulated inflammasome activation induced by T. cruzi on macrophages. Altogether, our results demonstrate that DMS, through anti-parasitic and immunomodulatory actions, can be beneficial in the treatment of chronic phase of T. cruzi infection and suggest that S1P-activated processes as possible therapeutic targets for the treatment of Chagas disease cardiomyopathy. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Universidade Salvador. Escola de Ciências da Saúde. Salvador, BA, Brasil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil | pt_BR |
| Affilliation | Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil | pt_BR |
| Affilliation | Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil | pt_BR |
| Affilliation | Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil | pt_BR |
| Affilliation | Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Universidade Federal de Bahia. Instituto de Ciências da Saúde. Departamento de Bioquímica e Biofísica. Salvador, BA, Brasil | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Centro de Ciências da Saúde. Rio de Janeiro, RJ, Brasil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
| Affilliation | Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil | pt_BR |
| Subject | Chagasic Cardiomyopathy | pt_BR |
| Subject | Chagas disease | pt_BR |
| Subject | Inflammatory disease | pt_BR |
| Subject | Trypanosoma cruzi | pt_BR |
| Subject | Treatment | pt_BR |
| Subject | Mice | pt_BR |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
