Oral Efficacy of Apigenin against Cutaneous Leishmaniasis: Involvement of Reactive Oxygen Species and Autophagy as a Mechanism of Action

Detalhes bibliográficos
Autor(a) principal: Silva, Fernanda Fonseca
Data de Publicação: 2016
Outros Autores: Inacio, Job D. F., 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/14643
Resumo: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil.
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spelling Silva, Fernanda FonsecaInacio, Job D. F.Cavalheiro, Marilene M. CantoMenna-Barreto, Rubem F. S.Amaral, Elmo E. Almeida2016-06-21T13:26:45Z2016-07-07T11:59:33Z2016-06-21T13:26:45Z2016-07-07T11:59:33Z2016SILVA, Fernanda Fonseca; et al. Oral Efficacy of Apigenin against Cutaneous Leishmaniasis: Involvement of Reactive Oxygen Species and Autophagy as a Mechanism of Action. PLoS Negl Trop Dis., v.10, n.2, e0004442, 16p, Feb. 2016.1935-2727https://www.arca.fiocruz.br/handle/icict/1464310.1371/journal.pntd.00044421935-2735engPublic Library of ScienceOral Efficacy of Apigenin against Cutaneous Leishmaniasis: Involvement of Reactive Oxygen Species and Autophagy as a Mechanism of Actioninfo: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 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.Background The treatment for leishmaniasis is currently based on pentavalent antimonials and amphotericin B; however, these drugs result in numerous adverse side effects. The lack of affordable therapy has necessitated the urgent development of new drugs that are efficacious, safe, and more accessible to patients. Natural products are a major source for the discovery of new and selective molecules for neglected diseases. In this paper, we evaluated the effect of apigenin on Leishmania amazonensis in vitro and in vivo and described the mechanism of action against intracellular amastigotes of L. amazonensis. Methodology/Principal Finding Apigenin reduced the infection index in a dose-dependent manner, with IC50 values of 4.3 μM and a selectivity index of 18.2. Apigenin induced ROS production in the L. amazonensis- infected macrophage, and the effects were reversed by NAC and GSH. Additionally, apigenin induced an increase in the number of macrophages autophagosomes after the infection, surrounding the parasitophorous vacuole, suggestive of the involvement of host autophagy probably due to ROS generation induced by apigenin. Furthermore, apigenin treatment was also effective in vivo, demonstrating oral bioavailability and reduced parasitic loads without altering serological toxicity markers. Conclusions/Significance In conclusion, our study suggests that apigenin exhibits leishmanicidal effects against L. amazonensis-infected macrophages. ROS production, as part of the mechanism of action, could occur through the increase in host autophagy and thereby promoting parasite death. Furthermore, our data suggest that apigenin is effective in the treatment of L. amazonensis-infected BALB/c mice by oral administration, without altering serological toxicity markers. The selective in vitro activity of apigenin, together with excellent theoretical predictions of oral availability, clear decreases in parasite load and lesion size, and no observed compromises to the overall health of the infected mice encourage us to supports further studies of apigenin as a candidate for the chemotherapeutic treatment of leishmaniasis.LeishmaniasisLeishmania amazonensisApigeninIn Vitro TechniquesApigeninaLeishmanioseTécnicas In VitroLeishmaniose Cutâneainfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZTEXTjob_inacio_etal_IOC_2016.PDF.txtjob_inacio_etal_IOC_2016.PDF.txtExtracted 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dc.title.pt_BR.fl_str_mv Oral Efficacy of Apigenin against Cutaneous Leishmaniasis: Involvement of Reactive Oxygen Species and Autophagy as a Mechanism of Action
title Oral Efficacy of Apigenin against Cutaneous Leishmaniasis: Involvement of Reactive Oxygen Species and Autophagy as a Mechanism of Action
spellingShingle Oral Efficacy of Apigenin against Cutaneous Leishmaniasis: Involvement of Reactive Oxygen Species and Autophagy as a Mechanism of Action
Silva, Fernanda Fonseca
Leishmaniasis
Leishmania amazonensis
Apigenin
In Vitro Techniques
Apigenina
Leishmaniose
Técnicas In Vitro
Leishmaniose Cutânea
title_short Oral Efficacy of Apigenin against Cutaneous Leishmaniasis: Involvement of Reactive Oxygen Species and Autophagy as a Mechanism of Action
title_full Oral Efficacy of Apigenin against Cutaneous Leishmaniasis: Involvement of Reactive Oxygen Species and Autophagy as a Mechanism of Action
title_fullStr Oral Efficacy of Apigenin against Cutaneous Leishmaniasis: Involvement of Reactive Oxygen Species and Autophagy as a Mechanism of Action
title_full_unstemmed Oral Efficacy of Apigenin against Cutaneous Leishmaniasis: Involvement of Reactive Oxygen Species and Autophagy as a Mechanism of Action
title_sort Oral Efficacy of Apigenin against Cutaneous Leishmaniasis: Involvement of Reactive Oxygen Species and Autophagy as a Mechanism of Action
author Silva, Fernanda Fonseca
author_facet Silva, Fernanda Fonseca
Inacio, Job D. F.
Cavalheiro, Marilene M. Canto
Menna-Barreto, Rubem F. S.
Amaral, Elmo E. Almeida
author_role author
author2 Inacio, Job D. F.
Cavalheiro, Marilene M. Canto
Menna-Barreto, Rubem F. S.
Amaral, Elmo E. Almeida
author2_role author
author
author
author
dc.contributor.author.fl_str_mv Silva, Fernanda Fonseca
Inacio, Job D. F.
Cavalheiro, Marilene M. Canto
Menna-Barreto, Rubem F. S.
Amaral, Elmo E. Almeida
dc.subject.en.pt_BR.fl_str_mv Leishmaniasis
Leishmania amazonensis
Apigenin
In Vitro Techniques
topic Leishmaniasis
Leishmania amazonensis
Apigenin
In Vitro Techniques
Apigenina
Leishmaniose
Técnicas In Vitro
Leishmaniose Cutânea
dc.subject.decs.pt_BR.fl_str_mv Apigenina
Leishmaniose
Técnicas In Vitro
Leishmaniose Cutânea
description Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil.
publishDate 2016
dc.date.accessioned.fl_str_mv 2016-06-21T13:26:45Z
2016-07-07T11:59:33Z
dc.date.available.fl_str_mv 2016-06-21T13:26:45Z
2016-07-07T11:59:33Z
dc.date.issued.fl_str_mv 2016
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. Oral Efficacy of Apigenin against Cutaneous Leishmaniasis: Involvement of Reactive Oxygen Species and Autophagy as a Mechanism of Action. PLoS Negl Trop Dis., v.10, n.2, e0004442, 16p, Feb. 2016.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/14643
dc.identifier.issn.pt_BR.fl_str_mv 1935-2727
dc.identifier.doi.pt_BR.fl_str_mv 10.1371/journal.pntd.0004442
dc.identifier.eissn.pt_BR.fl_str_mv 1935-2735
identifier_str_mv SILVA, Fernanda Fonseca; et al. Oral Efficacy of Apigenin against Cutaneous Leishmaniasis: Involvement of Reactive Oxygen Species and Autophagy as a Mechanism of Action. PLoS Negl Trop Dis., v.10, n.2, e0004442, 16p, Feb. 2016.
1935-2727
10.1371/journal.pntd.0004442
1935-2735
url https://www.arca.fiocruz.br/handle/icict/14643
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
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instacron_str FIOCRUZ
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collection Repositório Institucional da FIOCRUZ (ARCA)
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