Pterocarpanquinone LQB-118 Induces Apoptosis in Leishmania (Viannia) braziliensis and Controls Lesions in Infected Hamsters
Autor(a) principal: | |
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Data de Publicação: | 2014 |
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/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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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 |
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https://www.arca.fiocruz.br/handle/icict/10159 |
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eng |
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eng |
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info:eu-repo/semantics/openAccess |
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openAccess |
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Plos One |
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Plos One |
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