| Author | Nisimura, Lindice Mitie | |
| Author | Ferrão, Patricia Mello | |
| Author | Nogueira, Alanderson da Rocha | |
| Author | Waghabi, Mariana Caldas | |
| Author | Batista, Marcelo Meuser | |
| Author | Moreira, Otacilio C. | |
| Author | Urbina, Julio A. | |
| Author | Garzoni, Luciana Ribeiro | |
| Access date | 2020-12-18T18:52:41Z | |
| Available date | 2020-12-18T18:52:41Z | |
| Document date | 2020 | |
| Citation | NISIMURA, Lindice Mitie et al. Effect of Posaconazole in an in vitro model of cardiac fibrosis induced by Trypanosoma cruzi. Molecular and Biochemical Parasitology, v. 238, 111283, p. 1-9, June 2020. | pt_BR |
| ISSN | 0166-6851 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/45047 | |
| Language | eng | pt_BR |
| Publisher | Science Direct | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Cultura tridimensional | pt_BR |
| Subject in Portuguese | Proteína de matriz extracelular | pt_BR |
| Subject in Portuguese | Doença de Chagas | pt_BR |
| Subject in Portuguese | Posaconazole | pt_BR |
| Subject in Portuguese | Fibrose cardíaca | pt_BR |
| Subject in Portuguese | Microtissues cardíacas | pt_BR |
| Title | Effect of Posaconazole in an in vitro model of cardiac fibrosis induced by Trypanosoma cruzi | pt_BR |
| Type | Article | |
| DOI | 10.1016/j.molbiopara.2020.111283 | |
| Abstract | Posaconazole (POS) is an inhibitor of ergosterol biosynthesis in clinical use for treating invasive fungal infec-tions. POS has potent and selective anti-Trypanosoma cruzi activity and has been evaluated as a possible treat-ment for Chagas disease. Microtissues are a 3D culture system that has been shown to reproduce better tissue architecture and functionality than cell cultures in monolayer (2D). It has been used to evaluate chemotropic response as in vitro disease models. We previously developed an in vitro model that reproduces aspects of cardiac fibrosis observed in Chagas cardiomyopathy, using microtissues formed by primary cardiac cells infected by the T. cruzi, here called T. cruzi fibrotic cardiac microtissue (TCFCM). We also showed that the treatment of TCFCM with a TGF-β pathway inhibitor reduces fibrosis. Here, we aimed to evaluate the effect of POS in TCFCM, observing parasite load and molecules involved in fibrosis. To choose the concentration of POS to be used in TCFCM we first performed experiments in a monolayer of primary cardiac cell cultures and, based on the results, TCFCM was treated with 5 nM of POS for 96 h, starting at 144 h post-infection. Our previous studies showed that at this time the TCFCM had established fibrosis, resulting from T. cruzi infection. Treatment with POS of TCFCM reduced 50 % of parasite load as observed by real-time PCR and reduced markedly the fibrosis as observed by western blot and immunofluorescence, associated with a strong reduction in the expression of fibronectin and laminin (45 % and 54 %, respectively). POS treatment also changed the expression of proteins involved in the regulation of extracellular matrix proteins (TGF-β and TIMP-4, increased by 50 % and decreased by 58 %, respectively) in TCFCM. In conclusion, POS presented a potent trypanocidal effect both in 2D and in TCFCM, and the reduction of the parasite load was associated with a reduction of fibrosis in the absence of external im-munological effectors. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultra-estrutura Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | nstituto Venezolano de Investigaciones Cientificas. Caracas, Venezuela. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | Three-dimensional culture | pt_BR |
| Subject | Cardiac microtissues | pt_BR |
| Subject | Chagas Disease | pt_BR |
| Subject | Posaconazole | pt_BR |
| Subject | Cardiac fibrosis | pt_BR |
| Subject | Extracellular matrix protein | pt_BR |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
