Epigallocathechin-O-3-Gallate Inhibits Trypanothione Reductase of Leishmania infantum, Causing Alterations in Redox Balance and Leading to Parasite Death

Detalhes bibliográficos
Autor(a) principal: Inacio, Job D. F.
Data de Publicação: 2021
Outros Autores: Fonseca, Myslene S., Sousa, Gabriel Limaverde, Tomas, Ana M., Castro, Helena, 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/46985
Resumo: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatideos. Rio de Janeiro, RJ, Brasil.
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spelling Inacio, Job D. F.Fonseca, Myslene S.Sousa, Gabriel LimaverdeTomas, Ana M.Castro, HelenaAmaral, Elmo E. Almeida2021-04-30T18:08:37Z2021-04-30T18:08:37Z2021INACIO, Job D. F. et al. Epigallocathechin-O-3-Gallate Inhibits Trypanothione Reductase of Leishmania infantum, Causing Alterations in Redox Balance and Leading to Parasite Death. Front. Cell. Infect. Microbiol., v. 11, Article 640561, 11p, Mar. 2021.2235-2988https://www.arca.fiocruz.br/handle/icict/4698510.3389/fcimb.2021.640561engFrontiers MediaLeishmania infantumReductase trypanothioneMecanismo de açãoInibidor competitivoEGCGLeishmania infantumMechanism of actionTrypanothione reductaseCompetitive inhibitorEpigallocathechin-O-3-Gallate Inhibits Trypanothione Reductase of Leishmania infantum, Causing Alterations in Redox Balance and Leading to Parasite Deathinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatideos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatideos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Esquistossomose Experimental. Rio de Janeiro, RJ, Brasil.Universidade do Porto. i3S-Instituto de Investigação e Inovação em Saúde. Porto, Portugal / Universidade do Porto.CBAS-Instituto de Ciências Biomédicas Abel Salazar. Porto, Portugal.Universidade do Porto. i3S-Instituto de Investigação e Inovação em Saúde. Porto, PortugalFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatideos. Rio de Janeiro, RJ, Brasil.Leishmania infantum is a protozoan parasite that causes a vector borne infectious disease in humans known as visceral leishmaniasis (VL). This pathology, also caused by L. donovani, presently impacts the health of 500,000 people worldwide, and is treated with outdated anti-parasitic drugs that suffer from poor treatment regimens, severe side effects, high cost and/or emergence of resistant parasites. In previous works we have disclosed the anti-Leishmania activity of (-)-Epigallocatechin 3-O-gallate (EGCG), a flavonoid compound present in green tea leaves. To date, the mechanism of action of EGCG against Leishmania remains unknown. This work aims to shed new light into the leishmanicidal mode of action of EGCG. Towards this goal, we first confirmed that EGCG inhibits L. infantum promastigote proliferation in a concentration-dependent manner. Second, we established that the leishmanicidal effect of EGCG was associated with i) mitochondria depolarization and ii) decreased concentration of intracellular ATP, and iii) increased concentration of intracellular H2O2. Third, we found that the leishmanicidal effect and the elevated H2O2 levels induced by of EGCG can be abolished by PEG-catalase, strongly suggesting that this flavonoid kills L. infantum promastigotes by disturbing their intracellular redox balance. Finally, we gathered in silico and in vitro evidence that EGCG binds to trypanothione reductase (TR), a central enzyme of the redox homeostasis of Leishmania, acting as a competitive inhibitor of its trypanothione substrate.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/46985/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALJobInacio_ElmoAAmaral_etal_IOC_2021.pdfJobInacio_ElmoAAmaral_etal_IOC_2021.pdfapplication/pdf1626219https://www.arca.fiocruz.br/bitstream/icict/46985/2/JobInacio_ElmoAAmaral_etal_IOC_2021.pdf0d6d048c7775bceec7f1f6fa30ebb463MD52TEXTJobInacio_ElmoAAmaral_etal_IOC_2021.pdf.txtJobInacio_ElmoAAmaral_etal_IOC_2021.pdf.txtExtracted 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dc.title.pt_BR.fl_str_mv Epigallocathechin-O-3-Gallate Inhibits Trypanothione Reductase of Leishmania infantum, Causing Alterations in Redox Balance and Leading to Parasite Death
title Epigallocathechin-O-3-Gallate Inhibits Trypanothione Reductase of Leishmania infantum, Causing Alterations in Redox Balance and Leading to Parasite Death
spellingShingle Epigallocathechin-O-3-Gallate Inhibits Trypanothione Reductase of Leishmania infantum, Causing Alterations in Redox Balance and Leading to Parasite Death
Inacio, Job D. F.
Leishmania infantum
Reductase trypanothione
Mecanismo de ação
Inibidor competitivo
EGCG
Leishmania infantum
Mechanism of action
Trypanothione reductase
Competitive inhibitor
title_short Epigallocathechin-O-3-Gallate Inhibits Trypanothione Reductase of Leishmania infantum, Causing Alterations in Redox Balance and Leading to Parasite Death
title_full Epigallocathechin-O-3-Gallate Inhibits Trypanothione Reductase of Leishmania infantum, Causing Alterations in Redox Balance and Leading to Parasite Death
title_fullStr Epigallocathechin-O-3-Gallate Inhibits Trypanothione Reductase of Leishmania infantum, Causing Alterations in Redox Balance and Leading to Parasite Death
title_full_unstemmed Epigallocathechin-O-3-Gallate Inhibits Trypanothione Reductase of Leishmania infantum, Causing Alterations in Redox Balance and Leading to Parasite Death
title_sort Epigallocathechin-O-3-Gallate Inhibits Trypanothione Reductase of Leishmania infantum, Causing Alterations in Redox Balance and Leading to Parasite Death
author Inacio, Job D. F.
author_facet Inacio, Job D. F.
Fonseca, Myslene S.
Sousa, Gabriel Limaverde
Tomas, Ana M.
Castro, Helena
Amaral, Elmo E. Almeida
author_role author
author2 Fonseca, Myslene S.
Sousa, Gabriel Limaverde
Tomas, Ana M.
Castro, Helena
Amaral, Elmo E. Almeida
author2_role author
author
author
author
author
dc.contributor.author.fl_str_mv Inacio, Job D. F.
Fonseca, Myslene S.
Sousa, Gabriel Limaverde
Tomas, Ana M.
Castro, Helena
Amaral, Elmo E. Almeida
dc.subject.other.pt_BR.fl_str_mv Leishmania infantum
Reductase trypanothione
Mecanismo de ação
Inibidor competitivo
topic Leishmania infantum
Reductase trypanothione
Mecanismo de ação
Inibidor competitivo
EGCG
Leishmania infantum
Mechanism of action
Trypanothione reductase
Competitive inhibitor
dc.subject.en.pt_BR.fl_str_mv EGCG
Leishmania infantum
Mechanism of action
Trypanothione reductase
Competitive inhibitor
description Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatideos. Rio de Janeiro, RJ, Brasil.
publishDate 2021
dc.date.accessioned.fl_str_mv 2021-04-30T18:08:37Z
dc.date.available.fl_str_mv 2021-04-30T18:08:37Z
dc.date.issued.fl_str_mv 2021
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 INACIO, Job D. F. et al. Epigallocathechin-O-3-Gallate Inhibits Trypanothione Reductase of Leishmania infantum, Causing Alterations in Redox Balance and Leading to Parasite Death. Front. Cell. Infect. Microbiol., v. 11, Article 640561, 11p, Mar. 2021.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/46985
dc.identifier.issn.pt_BR.fl_str_mv 2235-2988
dc.identifier.doi.none.fl_str_mv 10.3389/fcimb.2021.640561
identifier_str_mv INACIO, Job D. F. et al. Epigallocathechin-O-3-Gallate Inhibits Trypanothione Reductase of Leishmania infantum, Causing Alterations in Redox Balance and Leading to Parasite Death. Front. Cell. Infect. Microbiol., v. 11, Article 640561, 11p, Mar. 2021.
2235-2988
10.3389/fcimb.2021.640561
url https://www.arca.fiocruz.br/handle/icict/46985
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 Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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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