DETC induces Leishmania parasite killing in human in vitro and murine in vivo models: a promising therapeutic alternative in Leishmaniasis.

Detalhes bibliográficos
Autor(a) principal: Cunha, Antonio Ricardo Khouri
Data de Publicação: 2010
Outros Autores: Novais, Fernanda Oliveira, Santana, Gisélia, Oliveira, Camila Indiani de, Santos, Marcos André Vannier dos, Barral, Aldina Maria Prado, Barral Netto, Manoel, Van Weyenbergh, Johan Jozef Rosa Maria
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/11003
Resumo: Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Microbiologia e Immunoregulação / Laboratório de Imunoparasitologia / Laboratório de Biologia Parasitária. Salvador, BA, Brasil
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spelling Cunha, Antonio Ricardo KhouriNovais, Fernanda OliveiraSantana, GiséliaOliveira, Camila Indiani deSantos, Marcos André Vannier dosBarral, Aldina Maria PradoBarral Netto, ManoelVan Weyenbergh, Johan Jozef Rosa Maria2015-06-29T17:59:50Z2015-06-29T17:59:50Z2010KHOURI, A. R. et al. DETC induces Leishmania parasite killing in human in vitro and murine in vivo models: a promising therapeutic alternative in Leishmaniasis. PLoS One, v. 5, n. 12, p. e14394, 2010.1932-6203https://www.arca.fiocruz.br/handle/icict/11003engPublic Library of ScienceDETC induces Leishmania parasite killing in human in vitro and murine in vivo models: a promising therapeutic alternative in Leishmaniasis.info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Microbiologia e Immunoregulação / Laboratório de Imunoparasitologia / Laboratório de Biologia Parasitária. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Microbiologia e Immunoregulação / Laboratório de Imunoparasitologia / Laboratório de Biologia Parasitária. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Microbiologia e Immunoregulação / Laboratório de Imunoparasitologia / Laboratório de Biologia Parasitária. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Microbiologia e Immunoregulação / Laboratório de Imunoparasitologia / Laboratório de Biologia Parasitária. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Microbiologia e Immunoregulação / Laboratório de Imunoparasitologia / Laboratório de Biologia Parasitária. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Microbiologia e Immunoregulação / Laboratório de Imunoparasitologia / Laboratório de Biologia Parasitária. Salvador, BA, Brasil / Institute for Investigation in Immunology. INCT. São Paulo, SP, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Microbiologia e Immunoregulação / Laboratório de Imunoparasitologia / Laboratório de Biologia Parasitária. Salvador, BA, Brasil / Institute for Investigation in Immunology. INCT. São Paulo, SP, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Microbiologia e Immunoregulação / Laboratório de Imunoparasitologia / Laboratório de Biologia Parasitária. Salvador, BA, Brasil / Institute for Investigation in Immunology. INCT. São Paulo, SP, BrasilBackground: Chemotherapy remains the primary tool for treatment and control of human leishmaniasis. However, currently available drugs present serious problems regarding side-effects, variable efficacy, and cost. Affordable and less toxic drugs are urgently needed for leishmaniasis. Methodology/Principal Findings: We demonstrate, by microscopy and viability assays, that superoxide dismutase inhibitor diethyldithiocarbamate (DETC) dose-dependently induces parasite killing (p,0.001) and is able to ‘‘sterilize’’ Leishmania amazonensis infection at 2 mM in human macrophages in vitro. We also show that DETC-induced superoxide production (p,0.001) and parasite destruction (p,0.05) were reverted by the addition of the antioxidant N-acetylcysteine, indicating that DETC-induced killing occurs through oxidative damage. Furthermore, ultrastructural analysis by electron microscopy demonstrates a rapid and highly selective destruction of amastigotes in the phagosome upon DETC treatment, without any apparent damage to the host cell, including its mitochondria. In addition, DETC significantly induced parasite killing in Leishmania promastigotes in axenic culture. In murine macrophages infected with Leishmania braziliensis, DETC significantly induced in vitro superoxide production (p = 0.0049) and parasite killing (p = 0.0043). In vivo treatment with DETC in BALB/C mice infected with Leishmania braziliensis caused a significant decrease in lesion size (p,0.0001), paralleled by a 100-fold decrease (p = 0.0087) in parasite burden. Conclusions/Significance: Due to its strong leishmanicidal effect in human macrophages in vitro, its in vivo effectiveness in a murine model, and its previously demonstrated in vivo safety profile in HIV treatment, DETC treatment might be considered as a valuable therapeutic option in human leishmaniasis, including HIV/Leishmania co-infection.Ditiocarb/farmacologiaLeishmania/efeitos de drogasLeishmania/metabolismoLeishmaniose/quimioterapiaAdjuvantes Imunológicos/farmacologiaAnimaisAntioxidantes/químicaApoptoseSobrevivência CelularHumanosMacrófagos/citologiaMacrófagos/metabolismoCamundongos TransgênicosCamundongos Endogâmicos BALB CMitocôndrias/metabolismoNecroseFagossomos/metabolismoinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82354https://www.arca.fiocruz.br/bitstream/icict/11003/1/license.txt8b4c200b4e10021c5683c6ccaba07169MD51ORIGINALKhouri, R DETC Induces....pdfKhouri, R DETC Induces....pdfapplication/pdf2463068https://www.arca.fiocruz.br/bitstream/icict/11003/2/Khouri%2c%20R%20DETC%20Induces....pdf149d412162140e1823da4614843403c6MD52TEXTKhouri, R DETC Induces....pdf.txtKhouri, R DETC Induces....pdf.txtExtracted texttext/plain41084https://www.arca.fiocruz.br/bitstream/icict/11003/3/Khouri%2c%20R%20DETC%20Induces....pdf.txtf336fa753e9782eba8261cd02d78754fMD53icict/110032023-03-15 14:33:18.992oai:www.arca.fiocruz.br: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Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-03-15T17:33:18Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv DETC induces Leishmania parasite killing in human in vitro and murine in vivo models: a promising therapeutic alternative in Leishmaniasis.
title DETC induces Leishmania parasite killing in human in vitro and murine in vivo models: a promising therapeutic alternative in Leishmaniasis.
spellingShingle DETC induces Leishmania parasite killing in human in vitro and murine in vivo models: a promising therapeutic alternative in Leishmaniasis.
Cunha, Antonio Ricardo Khouri
Ditiocarb/farmacologia
Leishmania/efeitos de drogas
Leishmania/metabolismo
Leishmaniose/quimioterapia
Adjuvantes Imunológicos/farmacologia
Animais
Antioxidantes/química
Apoptose
Sobrevivência Celular
Humanos
Macrófagos/citologia
Macrófagos/metabolismo
Camundongos Transgênicos
Camundongos Endogâmicos BALB C
Mitocôndrias/metabolismo
Necrose
Fagossomos/metabolismo
title_short DETC induces Leishmania parasite killing in human in vitro and murine in vivo models: a promising therapeutic alternative in Leishmaniasis.
title_full DETC induces Leishmania parasite killing in human in vitro and murine in vivo models: a promising therapeutic alternative in Leishmaniasis.
title_fullStr DETC induces Leishmania parasite killing in human in vitro and murine in vivo models: a promising therapeutic alternative in Leishmaniasis.
title_full_unstemmed DETC induces Leishmania parasite killing in human in vitro and murine in vivo models: a promising therapeutic alternative in Leishmaniasis.
title_sort DETC induces Leishmania parasite killing in human in vitro and murine in vivo models: a promising therapeutic alternative in Leishmaniasis.
author Cunha, Antonio Ricardo Khouri
author_facet Cunha, Antonio Ricardo Khouri
Novais, Fernanda Oliveira
Santana, Gisélia
Oliveira, Camila Indiani de
Santos, Marcos André Vannier dos
Barral, Aldina Maria Prado
Barral Netto, Manoel
Van Weyenbergh, Johan Jozef Rosa Maria
author_role author
author2 Novais, Fernanda Oliveira
Santana, Gisélia
Oliveira, Camila Indiani de
Santos, Marcos André Vannier dos
Barral, Aldina Maria Prado
Barral Netto, Manoel
Van Weyenbergh, Johan Jozef Rosa Maria
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Cunha, Antonio Ricardo Khouri
Novais, Fernanda Oliveira
Santana, Gisélia
Oliveira, Camila Indiani de
Santos, Marcos André Vannier dos
Barral, Aldina Maria Prado
Barral Netto, Manoel
Van Weyenbergh, Johan Jozef Rosa Maria
dc.subject.decs.pt_BR.fl_str_mv Ditiocarb/farmacologia
Leishmania/efeitos de drogas
Leishmania/metabolismo
Leishmaniose/quimioterapia
Adjuvantes Imunológicos/farmacologia
Animais
Antioxidantes/química
Apoptose
Sobrevivência Celular
Humanos
Macrófagos/citologia
Macrófagos/metabolismo
Camundongos Transgênicos
Camundongos Endogâmicos BALB C
Mitocôndrias/metabolismo
Necrose
Fagossomos/metabolismo
topic Ditiocarb/farmacologia
Leishmania/efeitos de drogas
Leishmania/metabolismo
Leishmaniose/quimioterapia
Adjuvantes Imunológicos/farmacologia
Animais
Antioxidantes/química
Apoptose
Sobrevivência Celular
Humanos
Macrófagos/citologia
Macrófagos/metabolismo
Camundongos Transgênicos
Camundongos Endogâmicos BALB C
Mitocôndrias/metabolismo
Necrose
Fagossomos/metabolismo
description Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Microbiologia e Immunoregulação / Laboratório de Imunoparasitologia / Laboratório de Biologia Parasitária. Salvador, BA, Brasil
publishDate 2010
dc.date.issued.fl_str_mv 2010
dc.date.accessioned.fl_str_mv 2015-06-29T17:59:50Z
dc.date.available.fl_str_mv 2015-06-29T17:59:50Z
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 KHOURI, A. R. et al. DETC induces Leishmania parasite killing in human in vitro and murine in vivo models: a promising therapeutic alternative in Leishmaniasis. PLoS One, v. 5, n. 12, p. e14394, 2010.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/11003
dc.identifier.issn.none.fl_str_mv 1932-6203
identifier_str_mv KHOURI, A. R. et al. DETC induces Leishmania parasite killing in human in vitro and murine in vivo models: a promising therapeutic alternative in Leishmaniasis. PLoS One, v. 5, n. 12, p. e14394, 2010.
1932-6203
url https://www.arca.fiocruz.br/handle/icict/11003
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)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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https://www.arca.fiocruz.br/bitstream/icict/11003/2/Khouri%2c%20R%20DETC%20Induces....pdf
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