Effect of Apigenin on Leishmania amazonensis Is Associated with Reactive Oxygen Species Production Followed by Mitochondrial Dysfunction

Detalhes bibliográficos
Autor(a) principal: Silva, Fernanda Fonseca
Data de Publicação: 2015
Outros Autores: Cavalheiro, Marilene M. Canto, Menna Barreto, Rubem F. S., Amaral, Elmo E. Almeida
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/11992
Resumo: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil.
id CRUZ_b3c28cf001e514c551e119548aab5769
oai_identifier_str oai:www.arca.fiocruz.br:icict/11992
network_acronym_str CRUZ
network_name_str Repositório Institucional da FIOCRUZ (ARCA)
repository_id_str 2135
spelling Silva, Fernanda FonsecaCavalheiro, Marilene M. CantoMenna Barreto, Rubem F. S.Amaral, Elmo E. Almeida2015-10-20T10:53:39Z2015-10-20T10:53:39Z2015SILVA, Fernanda Fonseca; et al. Effect of Apigenin on Leishmania amazonensis Is Associated with Reactive Oxygen Species Production Followed by Mitochondrial Dysfunction. Journal of Natural Products, v.78, n.4, p.880-884, 2015.0163-3864https://www.arca.fiocruz.br/handle/icict/1199210.1021/acs.jnatprod.5b00011engAmerican Chemical SocietyEffect of Apigenin on Leishmania amazonensis Is Associated with Reactive Oxygen Species Production Followed by Mitochondrial Dysfunctioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil.Leishmaniasis is an important neglected disease caused by protozoa of the genus Leishmania that affects more than 12 million people worldwide. Leishmaniasis treatment requires the administration of toxic and poorly tolerated drugs, and parasite resistance greatly reduces the efficacy of conventional medications. Apigenin (1), a naturally occurring plant flavone, has a wide range of reported biological effects. In this study, antileishmanial activity of 1 in vitro was investigated, and its mechanism of action against Leishmania amazonensis promastigotes was described. Treatment with 1 for 24 h resulted in concentration-dependent inhibition of cellular proliferation (IC50 = 23.7 μM) and increased reactive oxygen species (ROS) generation. Glutathione and N-acetyl-L-cysteine protected L. amazonensis from the effects of 1 and reduced ROS levels after the treatment. By contrast, oxidized glutathione did not reduce the levels of ROS caused by 1 by not preventing the proliferation inhibition. Apigenin 1 also induced an extensive swelling in parasite mitochondria, leading to an alteration of the mitochondrial membrane potential, rupture of the trans-Golgi network, and cytoplasmic vacuolization. These results demonstrate the leishmanicidal effect of 1 and suggest the involvement of ROS leading to mitochondrial collapse as part of the mechanism of action.Leishmania amazonensisMitochondrial DysfunctionApigeninTreatmentLeishmanioseApigeninainfo: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/11992/1/license.txt8b4c200b4e10021c5683c6ccaba07169MD51ORIGINALfernanda_silva_etal_IOC_2015.pdffernanda_silva_etal_IOC_2015.pdfapplication/pdf3831947https://www.arca.fiocruz.br/bitstream/icict/11992/2/fernanda_silva_etal_IOC_2015.pdf66f09a2ff56eb28882271dd922d1a61eMD52TEXTfernanda_silva_etal_IOC_2015.pdf.txtfernanda_silva_etal_IOC_2015.pdf.txtExtracted texttext/plain24954https://www.arca.fiocruz.br/bitstream/icict/11992/3/fernanda_silva_etal_IOC_2015.pdf.txt81a1b257756589757f771138571c1a46MD53icict/119922023-09-05 10:36:27.03oai:www.arca.fiocruz.br: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Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-09-05T13:36:27Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv Effect of Apigenin on Leishmania amazonensis Is Associated with Reactive Oxygen Species Production Followed by Mitochondrial Dysfunction
title Effect of Apigenin on Leishmania amazonensis Is Associated with Reactive Oxygen Species Production Followed by Mitochondrial Dysfunction
spellingShingle Effect of Apigenin on Leishmania amazonensis Is Associated with Reactive Oxygen Species Production Followed by Mitochondrial Dysfunction
Silva, Fernanda Fonseca
Leishmania amazonensis
Mitochondrial Dysfunction
Apigenin
Treatment
Leishmaniose
Apigenina
title_short Effect of Apigenin on Leishmania amazonensis Is Associated with Reactive Oxygen Species Production Followed by Mitochondrial Dysfunction
title_full Effect of Apigenin on Leishmania amazonensis Is Associated with Reactive Oxygen Species Production Followed by Mitochondrial Dysfunction
title_fullStr Effect of Apigenin on Leishmania amazonensis Is Associated with Reactive Oxygen Species Production Followed by Mitochondrial Dysfunction
title_full_unstemmed Effect of Apigenin on Leishmania amazonensis Is Associated with Reactive Oxygen Species Production Followed by Mitochondrial Dysfunction
title_sort Effect of Apigenin on Leishmania amazonensis Is Associated with Reactive Oxygen Species Production Followed by Mitochondrial Dysfunction
author Silva, Fernanda Fonseca
author_facet Silva, Fernanda Fonseca
Cavalheiro, Marilene M. Canto
Menna Barreto, Rubem F. S.
Amaral, Elmo E. Almeida
author_role author
author2 Cavalheiro, Marilene M. Canto
Menna Barreto, Rubem F. S.
Amaral, Elmo E. Almeida
author2_role author
author
author
dc.contributor.author.fl_str_mv Silva, Fernanda Fonseca
Cavalheiro, Marilene M. Canto
Menna Barreto, Rubem F. S.
Amaral, Elmo E. Almeida
dc.subject.en.pt_BR.fl_str_mv Leishmania amazonensis
Mitochondrial Dysfunction
Apigenin
Treatment
topic Leishmania amazonensis
Mitochondrial Dysfunction
Apigenin
Treatment
Leishmaniose
Apigenina
dc.subject.decs.pt_BR.fl_str_mv Leishmaniose
Apigenina
description Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil.
publishDate 2015
dc.date.accessioned.fl_str_mv 2015-10-20T10:53:39Z
dc.date.available.fl_str_mv 2015-10-20T10:53:39Z
dc.date.issued.fl_str_mv 2015
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 SILVA, Fernanda Fonseca; et al. Effect of Apigenin on Leishmania amazonensis Is Associated with Reactive Oxygen Species Production Followed by Mitochondrial Dysfunction. Journal of Natural Products, v.78, n.4, p.880-884, 2015.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/11992
dc.identifier.issn.none.fl_str_mv 0163-3864
dc.identifier.doi.none.fl_str_mv 10.1021/acs.jnatprod.5b00011
identifier_str_mv SILVA, Fernanda Fonseca; et al. Effect of Apigenin on Leishmania amazonensis Is Associated with Reactive Oxygen Species Production Followed by Mitochondrial Dysfunction. Journal of Natural Products, v.78, n.4, p.880-884, 2015.
0163-3864
10.1021/acs.jnatprod.5b00011
url https://www.arca.fiocruz.br/handle/icict/11992
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 American Chemical Society
publisher.none.fl_str_mv American Chemical Society
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)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/11992/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/11992/2/fernanda_silva_etal_IOC_2015.pdf
https://www.arca.fiocruz.br/bitstream/icict/11992/3/fernanda_silva_etal_IOC_2015.pdf.txt
bitstream.checksum.fl_str_mv 8b4c200b4e10021c5683c6ccaba07169
66f09a2ff56eb28882271dd922d1a61e
81a1b257756589757f771138571c1a46
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv repositorio.arca@fiocruz.br
_version_ 1813008825805963264

Registros relacionados