Pterocarpanquinone LQB-118 Induces Apoptosis in Leishmania (Viannia) braziliensis and Controls Lesions in Infected Hamsters

Detalhes bibliográficos
Autor(a) principal: Costa, Luciana
Data de Publicação: 2014
Outros Autores: Pinheiro, Roberta O, Dutra, Patrícia M. L, Santos, Rosiane F, Cunha Junior, Edézio F, Santos, Eduardo C. Torres, Silva, Alcides J. M. da, Costa, Paulo R. R, Silva, Silvia A. G. da
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/10159
Resumo: Universidade do Estado do Rio de Janeiro. Departamento de Microbiologia, Imunologia e Parasitologia. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
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network_name_str Repositório Institucional da FIOCRUZ (ARCA)
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spelling Costa, LucianaPinheiro, Roberta ODutra, Patrícia M. LSantos, Rosiane FCunha Junior, Edézio FSantos, Eduardo C. TorresSilva, Alcides J. M. daCosta, Paulo R. RSilva, Silvia A. G. da2015-05-04T16:34:30Z2015-05-04T16:34:30Z2014COSTA, Luciana. Pterocarpanquinone LQB-118 Induces Apoptosis in Leishmania (Viannia) braziliensis and Controls Lesions in Infected Hamsters. Plos One, v.9, n.10, 8p, 2014.https://www.arca.fiocruz.br/handle/icict/1015910.1371/journal.pone.0109672engPlos OneLeishmaniaCricetulusBrazilLeishmania (Viannia) braziliensisCricetulusBrasilCricetulusLeishmaniaBrasilPterocarpanquinone LQB-118 Induces Apoptosis in Leishmania (Viannia) braziliensis and Controls Lesions in Infected Hamstersinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade do Estado do Rio de Janeiro. Departamento de Microbiologia, Imunologia e Parasitologia. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Departamento de Microbiologia, Imunologia e Parasitologia. Laboratório de Bioquímica de Protozoários e Imunofisiologia do Exercício. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Departamento de Microbiologia, Imunologia e Parasitologia. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanossomatídeos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanossomatídeos. Rio de Janeiro, RJ, BrasilUniversidade Federal do Rio de Janeiro. Núcleo de Pesquisas de Produtos Naturais. Laboratório de Catálise Orgânica. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Núcleo de Pesquisas de Produtos Naturais. Laboratório de Química Bioorgânica. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Departamento de Microbiologia, Imunologia e Parasitologia. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Previous results demonstrate that the hybrid synthetic pterocarpanquinone LQB-118 presents antileishmanial activity against Leishmania amazonensis in a mouse model. The aim of the present study was to use a hamster model to investigate whether LQB-118 presents antileishmanial activity against Leishmania (Viannia) braziliensis, which is the major Leishmania species related to American tegumentary leishmaniasis. The in vitro antileishmanial activity of LQB-118 on L. braziliensis was tested on the promastigote and intracellular amastigote forms. The cell death induced by LQB-118 in the L. braziliensis promastigotes was analyzed using an annexin V-FITC/PI kit, the oxidative stress was evaluated by 29,79-dichlorodihydrofluorescein diacetate (H2DCFDA) and the ATP content by luminescence. In situ labeling of DNA fragments by terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) was used to investigate apoptosis in the intracellular amastigotes. L. braziliensis-infected hamsters were treated from the seventh day of infection with LQB-118 administered intralesionally (26 mg/kg/day, three times a week) or orally (4,3 mg/kg/day, five times a week) for eight weeks. LQB-118 was active against the L. braziliensis promastigotes and intracellular amastigotes, producing IC50 (50% inhibitory concentration) values of 3,460,1 and 7,560,8 mM, respectively. LQB-118 induced promastigote phosphatidylserine externalization accompanied by increased reactive oxygen species production and ATP depletion. Intracellular amastigote DNA fragmentation was also observed, without affecting the viability of macrophages. The treatment of L. braziliensisinfected hamsters with LQB-118, either orally or intralesionally, was effective in the control of lesion size, parasite load and increase intradermal reaction to parasite antigen. Taken together, these results show that the antileishmanial effect of LQB- 118 extends to L. braziliensis in the hamster model, involves the induction of parasite apoptosis and shows promising therapeutic option by oral or local routes in leishmaniasis.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txttext/plain1914https://www.arca.fiocruz.br/bitstream/icict/10159/1/license.txt7d48279ffeed55da8dfe2f8e81f3b81fMD51ORIGINALeduardo_santosetal_IOC_2014.pdfapplication/pdf661284https://www.arca.fiocruz.br/bitstream/icict/10159/2/eduardo_santosetal_IOC_2014.pdf28c8f5b253df75e3d946ff31a14aebe4MD52TEXTeduardo_santosetal_IOC_2014.pdf.txteduardo_santosetal_IOC_2014.pdf.txtExtracted texttext/plain38883https://www.arca.fiocruz.br/bitstream/icict/10159/3/eduardo_santosetal_IOC_2014.pdf.txtf9a2170367524561ec2d6bc170b5465bMD53icict/101592022-06-24 13:02:51.788oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352022-06-24T16:02:51Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv Pterocarpanquinone LQB-118 Induces Apoptosis in Leishmania (Viannia) braziliensis and Controls Lesions in Infected Hamsters
title Pterocarpanquinone LQB-118 Induces Apoptosis in Leishmania (Viannia) braziliensis and Controls Lesions in Infected Hamsters
spellingShingle Pterocarpanquinone LQB-118 Induces Apoptosis in Leishmania (Viannia) braziliensis and Controls Lesions in Infected Hamsters
Costa, Luciana
Leishmania
Cricetulus
Brazil
Leishmania (Viannia) braziliensis
Cricetulus
Brasil
Cricetulus
Leishmania
Brasil
title_short Pterocarpanquinone LQB-118 Induces Apoptosis in Leishmania (Viannia) braziliensis and Controls Lesions in Infected Hamsters
title_full Pterocarpanquinone LQB-118 Induces Apoptosis in Leishmania (Viannia) braziliensis and Controls Lesions in Infected Hamsters
title_fullStr Pterocarpanquinone LQB-118 Induces Apoptosis in Leishmania (Viannia) braziliensis and Controls Lesions in Infected Hamsters
title_full_unstemmed Pterocarpanquinone LQB-118 Induces Apoptosis in Leishmania (Viannia) braziliensis and Controls Lesions in Infected Hamsters
title_sort Pterocarpanquinone LQB-118 Induces Apoptosis in Leishmania (Viannia) braziliensis and Controls Lesions in Infected Hamsters
author Costa, Luciana
author_facet Costa, Luciana
Pinheiro, Roberta O
Dutra, Patrícia M. L
Santos, Rosiane F
Cunha Junior, Edézio F
Santos, Eduardo C. Torres
Silva, Alcides J. M. da
Costa, Paulo R. R
Silva, Silvia A. G. da
author_role author
author2 Pinheiro, Roberta O
Dutra, Patrícia M. L
Santos, Rosiane F
Cunha Junior, Edézio F
Santos, Eduardo C. Torres
Silva, Alcides J. M. da
Costa, Paulo R. R
Silva, Silvia A. G. da
author2_role author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Costa, Luciana
Pinheiro, Roberta O
Dutra, Patrícia M. L
Santos, Rosiane F
Cunha Junior, Edézio F
Santos, Eduardo C. Torres
Silva, Alcides J. M. da
Costa, Paulo R. R
Silva, Silvia A. G. da
dc.subject.other.pt_BR.fl_str_mv Leishmania
Cricetulus
Brazil
topic Leishmania
Cricetulus
Brazil
Leishmania (Viannia) braziliensis
Cricetulus
Brasil
Cricetulus
Leishmania
Brasil
dc.subject.en.pt_BR.fl_str_mv Leishmania (Viannia) braziliensis
Cricetulus
Brasil
dc.subject.es.pt_BR.fl_str_mv Cricetulus
Leishmania
Brasil
description Universidade do Estado do Rio de Janeiro. Departamento de Microbiologia, Imunologia e Parasitologia. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
publishDate 2014
dc.date.issued.fl_str_mv 2014
dc.date.accessioned.fl_str_mv 2015-05-04T16:34:30Z
dc.date.available.fl_str_mv 2015-05-04T16:34:30Z
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 COSTA, Luciana. Pterocarpanquinone LQB-118 Induces Apoptosis in Leishmania (Viannia) braziliensis and Controls Lesions in Infected Hamsters. Plos One, v.9, n.10, 8p, 2014.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/10159
dc.identifier.doi.pt_BR.fl_str_mv 10.1371/journal.pone.0109672
identifier_str_mv COSTA, Luciana. Pterocarpanquinone LQB-118 Induces Apoptosis in Leishmania (Viannia) braziliensis and Controls Lesions in Infected Hamsters. Plos One, v.9, n.10, 8p, 2014.
10.1371/journal.pone.0109672
url https://www.arca.fiocruz.br/handle/icict/10159
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 Plos One
publisher.none.fl_str_mv Plos One
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
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reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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