Chemotherapeutic Potential of 17-AAG againstCutaneous Leishmaniasis caused by Leishmania (Viannia) braziliensis

Detalhes bibliográficos
Autor(a) principal: Santos, Diego Moura
Data de Publicação: 2014
Outros Autores: Petersen, Antonio Luis de Oliveira Almeida, Celes, Fabiana Santana, Borges, Valeria de Matos, Veras, Patrícia Sampaio Tavares, Oliveira, Camila Indiani de
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/8817
Resumo: Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
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spelling Santos, Diego MouraPetersen, Antonio Luis de Oliveira AlmeidaCeles, Fabiana SantanaBorges, Valeria de MatosVeras, Patrícia Sampaio TavaresOliveira, Camila Indiani de2014-11-12T18:52:56Z2014-11-12T18:52:56Z2014SANTOS, D. M. et al. Chemotherapeutic Potential of 17-AAG againstCutaneous Leishmaniasis caused by Leishmania (Viannia) braziliensis. PLoS Neglected Tropical Diseases, v. 8, n. 10, p. e3275, 2014.1935-2727https://www.arca.fiocruz.br/handle/icict/881710.1371/journal.pntd.0003275engPublic Library of ScienceLeishmanioseLeishmaniose cutâneaLeishmaniose TegumentarLeishmania (Viannia) braziliensisSaúde públicaChemotherapeutic Potential of 17-AAG againstCutaneous Leishmaniasis caused by Leishmania (Viannia) braziliensisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia (iii-INCT). Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia (iii-INCT). Salvador, BA, BrasilBackground: Leishmaniasis remains a worldwide public health problem. The limited therapeutic options, drug toxicity and reports of resistance, reinforce the need for the development of new treatment options. Previously, we showed that 17- (allylamino)-17-demethoxygeldanamycin (17-AAG), a Heat Shock Protein 90 (HSP90)-specific inhibitor, reduces L. (L.) amazonensis infection in vitro. Herein, we expand the current knowledge on the leishmanicidal activity of 17-AAG against cutaneous leishmaniasis, employing an experimental model of infection with L. (V.) braziliensis. Methodology/Principal findings: Exposure of axenic L. (V.) braziliensis promastigotes to 17-AAG resulted in direct dosedependent parasite killing. These results were extended to L. (V.) braziliensis-infected macrophages, an effect that was dissociated from the production of nitric oxide (NO), superoxide (O22) or inflammatory mediators such as TNF-a, IL-6 and MCP-1. The leishmanicidal effect was then demonstrated in vivo, employing BALB/c mice infected with L. braziliensis. In this model, 17-AAG treatment resulted in smaller skin lesions and parasite counts were also significantly reduced. Lastly, 17-AAG showed a similar effect to amphotericin B regarding the ability to reduce parasite viability. Conclusion/Significance: 17-AAG effectively inhibited the growth of L. braziliensis, both in vitro and in vivo. Given the chronicity of L. (V.) braziliensis infection and its association with mucocutaneous leishmaniasis, 17-AAG can be envisaged as a new chemotherapeutic alternative for cutaneous Leishmaniasis.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-81914https://www.arca.fiocruz.br/bitstream/icict/8817/1/license.txt7d48279ffeed55da8dfe2f8e81f3b81fMD51ORIGINALSantos DM Chemotherapeutic....pdfSantos DM Chemotherapeutic....pdfapplication/pdf676143https://www.arca.fiocruz.br/bitstream/icict/8817/2/Santos%20DM%20Chemotherapeutic....pdf3284ff29fa9c02236cdba9382b528054MD52TEXTSantos DM Chemotherapeutic....pdf.txtSantos DM Chemotherapeutic....pdf.txtExtracted texttext/plain50782https://www.arca.fiocruz.br/bitstream/icict/8817/3/Santos%20DM%20Chemotherapeutic....pdf.txt8a59fb3f7df100821865d2935a197029MD53icict/88172023-03-15 14:33:03.092oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-03-15T17:33:03Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv Chemotherapeutic Potential of 17-AAG againstCutaneous Leishmaniasis caused by Leishmania (Viannia) braziliensis
title Chemotherapeutic Potential of 17-AAG againstCutaneous Leishmaniasis caused by Leishmania (Viannia) braziliensis
spellingShingle Chemotherapeutic Potential of 17-AAG againstCutaneous Leishmaniasis caused by Leishmania (Viannia) braziliensis
Santos, Diego Moura
Leishmaniose
Leishmaniose cutânea
Leishmaniose Tegumentar
Leishmania (Viannia) braziliensis
Saúde pública
title_short Chemotherapeutic Potential of 17-AAG againstCutaneous Leishmaniasis caused by Leishmania (Viannia) braziliensis
title_full Chemotherapeutic Potential of 17-AAG againstCutaneous Leishmaniasis caused by Leishmania (Viannia) braziliensis
title_fullStr Chemotherapeutic Potential of 17-AAG againstCutaneous Leishmaniasis caused by Leishmania (Viannia) braziliensis
title_full_unstemmed Chemotherapeutic Potential of 17-AAG againstCutaneous Leishmaniasis caused by Leishmania (Viannia) braziliensis
title_sort Chemotherapeutic Potential of 17-AAG againstCutaneous Leishmaniasis caused by Leishmania (Viannia) braziliensis
author Santos, Diego Moura
author_facet Santos, Diego Moura
Petersen, Antonio Luis de Oliveira Almeida
Celes, Fabiana Santana
Borges, Valeria de Matos
Veras, Patrícia Sampaio Tavares
Oliveira, Camila Indiani de
author_role author
author2 Petersen, Antonio Luis de Oliveira Almeida
Celes, Fabiana Santana
Borges, Valeria de Matos
Veras, Patrícia Sampaio Tavares
Oliveira, Camila Indiani de
author2_role author
author
author
author
author
dc.contributor.author.fl_str_mv Santos, Diego Moura
Petersen, Antonio Luis de Oliveira Almeida
Celes, Fabiana Santana
Borges, Valeria de Matos
Veras, Patrícia Sampaio Tavares
Oliveira, Camila Indiani de
dc.subject.other.pt_BR.fl_str_mv Leishmaniose
Leishmaniose cutânea
Leishmaniose Tegumentar
Leishmania (Viannia) braziliensis
Saúde pública
topic Leishmaniose
Leishmaniose cutânea
Leishmaniose Tegumentar
Leishmania (Viannia) braziliensis
Saúde pública
description Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
publishDate 2014
dc.date.accessioned.fl_str_mv 2014-11-12T18:52:56Z
dc.date.available.fl_str_mv 2014-11-12T18:52:56Z
dc.date.issued.fl_str_mv 2014
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv SANTOS, D. M. et al. Chemotherapeutic Potential of 17-AAG againstCutaneous Leishmaniasis caused by Leishmania (Viannia) braziliensis. PLoS Neglected Tropical Diseases, v. 8, n. 10, p. e3275, 2014.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/8817
dc.identifier.issn.none.fl_str_mv 1935-2727
dc.identifier.doi.none.fl_str_mv 10.1371/journal.pntd.0003275
identifier_str_mv SANTOS, D. M. et al. Chemotherapeutic Potential of 17-AAG againstCutaneous Leishmaniasis caused by Leishmania (Viannia) braziliensis. PLoS Neglected Tropical Diseases, v. 8, n. 10, p. e3275, 2014.
1935-2727
10.1371/journal.pntd.0003275
url https://www.arca.fiocruz.br/handle/icict/8817
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
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reponame_str Repositório Institucional da FIOCRUZ (ARCA)
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