| Author | Lopes, Mariana Eduarda Aparecida de Souza Assunção | |
| Author | Ribeiro, Juliana Martins | |
| Author | Carvalho, Andréa Teixeira de | |
| Author | Murta, Silvane Maria Fonseca | |
| Author | Souza-Fagundes, Elaine M. | |
| Access date | 2023-03-15T18:35:00Z | |
| Available date | 2023-03-15T18:35:00Z | |
| Document date | 2023 | |
| Citation | LOPES, Mariana Eduarda Aparecida de Souza Assunção et al. A functional assay using human whole blood and flow cytometry analysis to evaluate cytotoxicity and immunomodulatory effect of anti-Trypanosoma cruzi drugs. Experimental Parasitology, 247, p. 1-8, 108490, Feb. 2023. | en_US |
| ISSN | 0014-4894 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/57389 | |
| Language | eng | en_US |
| Publisher | Academic Press | en_US |
| Rights | restricted access | |
| Title | A functional assay using human whole blood and flow cytometry analysis to evaluate cytotoxicity and immunomodulatory effect of anti-Trypanosoma cruzi drugs | en_US |
| Type | Article | |
| DOI | 10.1016/j.exppara.2023.108490 | |
| Abstract | The discovery and development of new drugs for the treatment of Chagas disease is urgent due to the high toxicity and low cure efficacy, mainly during the chronic phase of this disease. Other chemotherapeutic approaches for Chagas disease treatment are being researched and require screening assays suitable for evaluating the effectivity of new biologically active compounds. This study aims to evaluate a functional assay using the internalization of epimastigotes forms of Trypanosoma cruzi by human peripheral blood leukocytes from healthy volunteers and analyses by flow cytometry of cytotoxicity, anti-T. cruzi activity, and immunomodulatory effect of benznidazole, ravuconazole, and posaconazole. The culture supernatant was used to measure cytokines (IL-1-β, IL-6, INF-γ, TNF and IL-10) and chemokines (MCP-1/CCL2, CCL5/RANTES and CXCL8/IL-8). The data showed a reduction in the internalization of T. cruzi epimastigote forms treated with ravuconazole, demonstrating its potential anti-T. cruzi activity. In addition, an increased amount of IL-10 and TNF cytokines was observed in the supernatant of cultures upon the addition of the drug, mainly IL-10 in the presence of benznidazole, ravuconazole and posaconazole, and TNF in the presence of ravuconazole and posaconazole. Moreover, the results revealed a decrease in the MCP-1/CCL2 index in cultures in the presence of benznidazole, ravuconazole, and posaconazole. A decrease in the CCL5/RANTES and CXCL8/IL-8 index in cultures with BZ, when compared to the culture without drugs, was also observed. In conclusion, the innovative functional test proposed in this study may be a valuable tool as a confirmatory test for selecting promising compounds identified in prospecting programs for new drugs for Chagas disease treatment. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Genômica Funcional de Parasitos. Belo Horizonte, MG, Brazil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Genômica Funcional de Parasitos. Belo Horizonte, MG, Brazil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisas em Biomarcadores. Belo Horizonte, MG, Brazil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Genômica Funcional de Parasitos. Belo Horizonte, MG, Brazil. | en_US |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Genética, Ecologia e Evolução. Belo Horizonte, MG, Brazil. | en_US |
| Subject | Chagas disease | en_US |
| Subject | Chemokines | en_US |
| Subject | Cytokines | en_US |
| Subject | Flow cytometry | en_US |
| Subject | Trypanosoma cruzi | en_US |
| Subject | Whole blood | en_US |
| Embargo date | 2099-12-31 | |
