17-AAG Kills Intracellular Leishmania amazonensis while Reducing Inflammatory Responses in Infected Macrophages

Detalhes bibliográficos
Autor(a) principal: Petersen, Antonio Luis de Oliveira Almeida
Data de Publicação: 2012
Outros Autores: Guedes, Carlos Eduardo Sampaio, Versoza, Carolina Leite, Lima, José Geraldo Bomfim, Freitas, Luiz Antônio Rodrigues de, Borges, Valéria de Matos, Veras, Patrícia Sampaio Tavares
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UFBA
Texto Completo: http://repositorio.ufba.br/ri/handle/ri/18170
Resumo: p. 1-12
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spelling Petersen, Antonio Luis de Oliveira AlmeidaGuedes, Carlos Eduardo SampaioVersoza, Carolina LeiteLima, José Geraldo BomfimFreitas, Luiz Antônio Rodrigues deBorges, Valéria de MatosVeras, Patrícia Sampaio TavaresPetersen, Antonio Luis de Oliveira AlmeidaGuedes, Carlos Eduardo SampaioVersoza, Carolina LeiteLima, José Geraldo BomfimFreitas, Luiz Antônio Rodrigues deBorges, Valéria de MatosVeras, Patrícia Sampaio Tavares2015-10-27T14:55:15Z2015-10-27T14:55:15Z20121932-6203http://repositorio.ufba.br/ri/handle/ri/18170v. 7, n. 11p. 1-12Background: Leishmaniasis is a neglected endemic disease with a broad spectrum of clinical manifestations. Pentavalent antimonials have been the treatment of choice for the past 70 years and, due to the emergence of resistant cases, the efficacy of these drugs has come under scrutiny. Second-line drugs are less efficacious, cause a range of side effects and can be costly. The formulation of new generations of drugs, especially in developing countries, has become mandatory. Methodology/Principal Findings: We investigated the anti-leishmanial effect of 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), an HSP90 inhibitor, in vitro. This inhibitor is currently in clinical trials for cancer treatment; however, its effects against intracellular Leishmania remain untested. Macrophages infected with L. amazonensis were treated with 17-AAG (25–500 nM) and parasite load was quantified using optical microscopy. Parasite load declined in 17-AAG-treated macrophages in a dose- and time-dependent manner. Intracellular parasite death became irreversible after 4 h of treatment with 17-AAG, and occurred independent of nitric oxide (NO) and superoxide (O2−) production. Additionally, intracellular parasite viability was severely reduced after 48 h of treatment. Interestingly, treatment with 17-AAG reduced pro-inflammatory mediator production, including TNF-α, IL-6 and MCP-1, yet IL-12 remained unaffected. Electron microscopy revealed morphological alterations, such as double-membrane vacuoles and myelin figures at 24 and 48 h after 17-AAG treatment. Conclusions/Significance: The HSP90 inhibitor, 17-AAG, possesses high potency under low dosage and reduces both pro-inflammatory and oxidative molecule production. Therefore, further studies are warranted to investigate this inhibitor’s potential in the development of new generations of anti-leishmanials.Submitted by Edileide Reis (leyde-landy@hotmail.com) on 2014-05-06T17:48:33Z No. of bitstreams: 1 José Geraldo Bomfim Lima.pdf: 951776 bytes, checksum: 5eb8ffba084287284d06b02e0e0a5ba0 (MD5)Approved for entry into archive by Flávia Ferreira (flaviaccf@yahoo.com.br) on 2015-10-27T14:55:15Z (GMT) No. of bitstreams: 1 José Geraldo Bomfim Lima.pdf: 951776 bytes, checksum: 5eb8ffba084287284d06b02e0e0a5ba0 (MD5)Made available in DSpace on 2015-10-27T14:55:15Z (GMT). No. of bitstreams: 1 José Geraldo Bomfim Lima.pdf: 951776 bytes, checksum: 5eb8ffba084287284d06b02e0e0a5ba0 (MD5) Previous issue date: 2012http://dx.doi.org/ 10.1371/journal.pone.0049496reponame:Repositório Institucional da UFBAinstname:Universidade Federal da Bahia (UFBA)instacron:UFBALeishmaniaMacrophagesEndemic Diseases17-AAG Kills Intracellular Leishmania amazonensis while Reducing Inflammatory Responses in Infected MacrophagesPLoS ONEinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleBrasilinfo:eu-repo/semantics/openAccessengORIGINALJosé Geraldo Bomfim Lima.pdfJosé Geraldo Bomfim Lima.pdfapplication/pdf951776https://repositorio.ufba.br/bitstream/ri/18170/1/Jos%c3%a9%20Geraldo%20Bomfim%20Lima.pdf5eb8ffba084287284d06b02e0e0a5ba0MD51LICENSElicense.txtlicense.txttext/plain1345https://repositorio.ufba.br/bitstream/ri/18170/2/license.txt0d4b811ef71182510d2015daa7c8a900MD52TEXTJosé Geraldo Bomfim Lima.pdf.txtJosé Geraldo Bomfim Lima.pdf.txtExtracted texttext/plain61486https://repositorio.ufba.br/bitstream/ri/18170/3/Jos%c3%a9%20Geraldo%20Bomfim%20Lima.pdf.txt20c6f1c26d869b6e69b73bf7b6fd2f7fMD53ri/181702022-08-26 11:03:23.743oai:repositorio.ufba.br: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Repositório InstitucionalPUBhttp://192.188.11.11:8080/oai/requestopendoar:19322022-08-26T14:03:23Repositório Institucional da UFBA - Universidade Federal da Bahia (UFBA)false
dc.title.pt_BR.fl_str_mv 17-AAG Kills Intracellular Leishmania amazonensis while Reducing Inflammatory Responses in Infected Macrophages
dc.title.alternative.pt_BR.fl_str_mv PLoS ONE
title 17-AAG Kills Intracellular Leishmania amazonensis while Reducing Inflammatory Responses in Infected Macrophages
spellingShingle 17-AAG Kills Intracellular Leishmania amazonensis while Reducing Inflammatory Responses in Infected Macrophages
Petersen, Antonio Luis de Oliveira Almeida
Leishmania
Macrophages
Endemic Diseases
title_short 17-AAG Kills Intracellular Leishmania amazonensis while Reducing Inflammatory Responses in Infected Macrophages
title_full 17-AAG Kills Intracellular Leishmania amazonensis while Reducing Inflammatory Responses in Infected Macrophages
title_fullStr 17-AAG Kills Intracellular Leishmania amazonensis while Reducing Inflammatory Responses in Infected Macrophages
title_full_unstemmed 17-AAG Kills Intracellular Leishmania amazonensis while Reducing Inflammatory Responses in Infected Macrophages
title_sort 17-AAG Kills Intracellular Leishmania amazonensis while Reducing Inflammatory Responses in Infected Macrophages
author Petersen, Antonio Luis de Oliveira Almeida
author_facet Petersen, Antonio Luis de Oliveira Almeida
Guedes, Carlos Eduardo Sampaio
Versoza, Carolina Leite
Lima, José Geraldo Bomfim
Freitas, Luiz Antônio Rodrigues de
Borges, Valéria de Matos
Veras, Patrícia Sampaio Tavares
author_role author
author2 Guedes, Carlos Eduardo Sampaio
Versoza, Carolina Leite
Lima, José Geraldo Bomfim
Freitas, Luiz Antônio Rodrigues de
Borges, Valéria de Matos
Veras, Patrícia Sampaio Tavares
author2_role author
author
author
author
author
author
dc.contributor.author.fl_str_mv Petersen, Antonio Luis de Oliveira Almeida
Guedes, Carlos Eduardo Sampaio
Versoza, Carolina Leite
Lima, José Geraldo Bomfim
Freitas, Luiz Antônio Rodrigues de
Borges, Valéria de Matos
Veras, Patrícia Sampaio Tavares
Petersen, Antonio Luis de Oliveira Almeida
Guedes, Carlos Eduardo Sampaio
Versoza, Carolina Leite
Lima, José Geraldo Bomfim
Freitas, Luiz Antônio Rodrigues de
Borges, Valéria de Matos
Veras, Patrícia Sampaio Tavares
dc.subject.por.fl_str_mv Leishmania
Macrophages
Endemic Diseases
topic Leishmania
Macrophages
Endemic Diseases
description p. 1-12
publishDate 2012
dc.date.issued.fl_str_mv 2012
dc.date.accessioned.fl_str_mv 2015-10-27T14:55:15Z
dc.date.available.fl_str_mv 2015-10-27T14:55:15Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.uri.fl_str_mv http://repositorio.ufba.br/ri/handle/ri/18170
dc.identifier.issn.none.fl_str_mv 1932-6203
dc.identifier.number.pt_BR.fl_str_mv v. 7, n. 11
identifier_str_mv 1932-6203
v. 7, n. 11
url http://repositorio.ufba.br/ri/handle/ri/18170
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.country.fl_str_mv Brasil
dc.source.pt_BR.fl_str_mv http://dx.doi.org/ 10.1371/journal.pone.0049496
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFBA
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