In vitro evaluation of the anti-leishmanial activity and toxicity of PK11195
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2018 |
| Outros Autores: | , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/25026 |
Resumo: | FAPESB, CNPq. |
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Guedes, Carlos Eduardo SampaioDias, Beatriz Rocha SimõesPetersen, Antonio Luis de Oliveira AlmeidaCruz, Kercia PinheiroAlmeida, Niara de JesusAndrade, Daniela RodriguesMenezes, Juliana Perrone Bezerra deBorges, Valéria de MatosVeras, Patrícia Sampaio Tavares2018-03-01T17:51:53Z2018-03-01T17:51:53Z2018GUEDES, C. E. S. et al. In vitro evaluation of the anti-leishmanial activity and toxicity of PK11195. Memórias do Instituto Oswaldo Cruz, v. 113, n. 4, p. e170345, 2018.0074-0276https://www.arca.fiocruz.br/handle/icict/2502610.1590/0074-02760170345FAPESB, CNPq.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Patologia e Biointervenção. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Patologia e Biointervenção. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Patologia e Biointervenção. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Patologia e Biointervenção. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Patologia e Biointervenção. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório Integrado de Microbiologia e Imunoregulação. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Patologia e Biointervenção. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório Integrado de Microbiologia e Imunoregulação. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Patologia e Biointervenção. Salvador, BA, BrasilLeishmaniasis, one of the most neglected diseases, is a serious public health problem in many countries, including Brazil. Currently available treatments require long-term use and have serious side effects, necessitating the development of new therapeutic interventions. Because translocator protein (TSPO) levels are reduced in Leishmania amazonensis-infected cells and because this protein participates in apoptosis and immunomodulation, TSPO represents a potential target for Leishmania chemotherapy. The present study evaluated PK11195, a ligand of this protein, as an anti-leishmanial agent. OBJECTIVE To evaluate the leishmanicidal activity of PK11195 against L. amazonensis in infected CBA mouse macrophages in vitro. METHODS The viability of axenic L. amazonensis, Leishmania major, and Leishmania braziliensis promastigotes was assessed after 48 h treatment with PK11195 (0.2-400 μM). Additionally, intracellular parasite viability was evaluated to determine IC50 values and the number of viable parasites in infected macrophages treated with PK11195 (50-100 μM). Infected macrophages were then treated with PK11195 (25-100 μM) to determine the percentage of L. amazonensis-infected cells and the number of parasites per infected cell. Electron microscopy was used to investigate morphological changes caused by PK11195. The production of free oxygen radicals, nitric oxide, and pro-inflammatory cytokines was also evaluated in infected macrophages treated with PK11195 and primed or not primed with IFN-γ. FINDINGS Median IC50 values for PK11195 were 14.2 μM for L. amazonensis, 8.2 μM for L. major, and 3.5 μM for L. braziliensis. The selective index value for L. amazonensis was 13.7, indicating the safety of PK11195 for future testing in mammals. Time- and dose-dependent reductions in the percentage of infected macrophages, the number of parasites per infected macrophage, and the number of viable intracellular parasites were observed. Electron microscopy revealed some morphological alterations suggestive of autophagy. Interestingly, MCP-1 and superoxide levels were reduced in L. amazonensis-infected macrophages treated with PK11195. MAIN CONCLUSIONS PK11195 causes the killing of amastigotes in vitro by mechanisms independent of inflammatory mediators and causes morphological alterations within Leishmania parasites, suggestive of autophagy, at doses that are non-toxic to macrophages. Thus, this molecule has demonstrated potential as an anti-leishmanial agent.engInstituto Oswaldo CruzPK11195Leishmania amazonensisMacrófagosQuimioterapiaPK11195Leishmania amazonensis -MacrophagesChemotherapyIn vitro evaluation of the anti-leishmanial activity and toxicity of PK11195info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/25026/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALGuedes CS In vitro evaluation of antileishmanial activity ....pdfGuedes CS In vitro evaluation of antileishmanial activity ....pdfapplication/pdf1265052https://www.arca.fiocruz.br/bitstream/icict/25026/2/Guedes%20CS%20In%20vitro%20evaluation%20of%20antileishmanial%20activity%20....pdfea34f4207175b7991dbeadfe6793821fMD52TEXTGuedes CS In 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| dc.title.pt_BR.fl_str_mv |
In vitro evaluation of the anti-leishmanial activity and toxicity of PK11195 |
| title |
In vitro evaluation of the anti-leishmanial activity and toxicity of PK11195 |
| spellingShingle |
In vitro evaluation of the anti-leishmanial activity and toxicity of PK11195 Guedes, Carlos Eduardo Sampaio PK11195 Leishmania amazonensis Macrófagos Quimioterapia PK11195 Leishmania amazonensis - Macrophages Chemotherapy |
| title_short |
In vitro evaluation of the anti-leishmanial activity and toxicity of PK11195 |
| title_full |
In vitro evaluation of the anti-leishmanial activity and toxicity of PK11195 |
| title_fullStr |
In vitro evaluation of the anti-leishmanial activity and toxicity of PK11195 |
| title_full_unstemmed |
In vitro evaluation of the anti-leishmanial activity and toxicity of PK11195 |
| title_sort |
In vitro evaluation of the anti-leishmanial activity and toxicity of PK11195 |
| author |
Guedes, Carlos Eduardo Sampaio |
| author_facet |
Guedes, Carlos Eduardo Sampaio Dias, Beatriz Rocha Simões Petersen, Antonio Luis de Oliveira Almeida Cruz, Kercia Pinheiro Almeida, Niara de Jesus Andrade, Daniela Rodrigues Menezes, Juliana Perrone Bezerra de Borges, Valéria de Matos Veras, Patrícia Sampaio Tavares |
| author_role |
author |
| author2 |
Dias, Beatriz Rocha Simões Petersen, Antonio Luis de Oliveira Almeida Cruz, Kercia Pinheiro Almeida, Niara de Jesus Andrade, Daniela Rodrigues Menezes, Juliana Perrone Bezerra de Borges, Valéria de Matos Veras, Patrícia Sampaio Tavares |
| author2_role |
author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Guedes, Carlos Eduardo Sampaio Dias, Beatriz Rocha Simões Petersen, Antonio Luis de Oliveira Almeida Cruz, Kercia Pinheiro Almeida, Niara de Jesus Andrade, Daniela Rodrigues Menezes, Juliana Perrone Bezerra de Borges, Valéria de Matos Veras, Patrícia Sampaio Tavares |
| dc.subject.other.pt_BR.fl_str_mv |
PK11195 Leishmania amazonensis Macrófagos Quimioterapia |
| topic |
PK11195 Leishmania amazonensis Macrófagos Quimioterapia PK11195 Leishmania amazonensis - Macrophages Chemotherapy |
| dc.subject.en.pt_BR.fl_str_mv |
PK11195 Leishmania amazonensis - Macrophages Chemotherapy |
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FAPESB, CNPq. |
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2018 |
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2018-03-01T17:51:53Z |
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2018-03-01T17:51:53Z |
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2018 |
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GUEDES, C. E. S. et al. In vitro evaluation of the anti-leishmanial activity and toxicity of PK11195. Memórias do Instituto Oswaldo Cruz, v. 113, n. 4, p. e170345, 2018. |
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https://www.arca.fiocruz.br/handle/icict/25026 |
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0074-0276 |
| dc.identifier.doi.none.fl_str_mv |
10.1590/0074-02760170345 |
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GUEDES, C. E. S. et al. In vitro evaluation of the anti-leishmanial activity and toxicity of PK11195. Memórias do Instituto Oswaldo Cruz, v. 113, n. 4, p. e170345, 2018. 0074-0276 10.1590/0074-02760170345 |
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