Synergistic antileishmanial effect of oregano essential oil and silver nanoparticles: mechanisms of action on Leishmania amazonensis

Detalhes bibliográficos
Autor(a) principal: Alves, Alex Barbosa
Data de Publicação: 2023
Outros Autores: Bortoleti, Bruna Taciane da Silva, Tomiotto-Pellissier, Fernanda, Ganaza, Ana Flávia Marques, Gonçalves, Manoela Daiele, Carloto, Amanda Cristina Machado, Rodrigues, Ana Carolina Jacob, Silva, Taylon Felipe, Nakazato, Gerson, Kobayashi, Renata Katsuko Takayama, Lazarin-Bidóia, Danielle, Miranda-Sapla, Milena Menegazzo, Costa, Idessania Nazareth, Pavanelli, Wander Rogério, Conchon-Costa, Ivete
Tipo de documento: Artigo
Idioma: por
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/59223
https://doi.org/10.3390/ pathogens12050660
Resumo: Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Ciências Patológicas. Laboratório de Imunoparasitologia de Doenças Negligenciadas e Câncer. Londrina, PR, Brasil.
id CRUZ_df94e8a6b7ddac5c6fbff8547ffe8eb4
oai_identifier_str oai:www.arca.fiocruz.br:icict/59223
network_acronym_str CRUZ
network_name_str Repositório Institucional da FIOCRUZ (ARCA)
repository_id_str 2135
spelling Alves, Alex BarbosaBortoleti, Bruna Taciane da SilvaTomiotto-Pellissier, FernandaGanaza, Ana Flávia MarquesGonçalves, Manoela DaieleCarloto, Amanda Cristina MachadoRodrigues, Ana Carolina JacobSilva, Taylon FelipeNakazato, GersonKobayashi, Renata Katsuko TakayamaLazarin-Bidóia, DanielleMiranda-Sapla, Milena MenegazzoCosta, Idessania NazarethPavanelli, Wander RogérioConchon-Costa, Ivete2023-06-28T16:01:56Z2023-06-28T16:01:56Z2023ALVES, Alex Barbosa et al. Synergistic antileishmanial effect of oregano essential oil and silver nanoparticles: mechanisms of action on Leishmania amazonensis. Pathogens, v. 12, n. 660, p. 1-17, 2023.2076-0817https://www.arca.fiocruz.br/handle/icict/59223https://doi.org/10.3390/ pathogens12050660porMDPIOriganumLeishmaniasisPlant OilsApoptosisAntileishmaniasisAceites de PlantasHuiles végétalesLeishmanioseOrégano (Planta)Óleos de PlantasApoptoseAntileishmanioseSynergistic antileishmanial effect of oregano essential oil and silver nanoparticles: mechanisms of action on Leishmania amazonensisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Ciências Patológicas. Laboratório de Imunoparasitologia de Doenças Negligenciadas e Câncer. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Ciências Patológicas. Laboratório de Imunoparasitologia de Doenças Negligenciadas e Câncer. Londrina, PR, Brasil. / Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Ciências Patológicas. Laboratório de Imunoparasitologia de Doenças Negligenciadas e Câncer. Londrina, PR, Brasil. / Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Ciências Patológicas. Laboratório de Imunoparasitologia de Doenças Negligenciadas e Câncer. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Exatas. Departamento de Química. Laboratório de Biotransformação e Fitoquímica. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Ciências Patológicas. Laboratório de Imunoparasitologia de Doenças Negligenciadas e Câncer. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Ciências Patológicas. Laboratório de Imunoparasitologia de Doenças Negligenciadas e Câncer. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Ciências Patológicas. Laboratório de Imunoparasitologia de Doenças Negligenciadas e Câncer. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Microbiologia. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Microbiologia. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Ciências Patológicas. Laboratório de Imunoparasitologia de Doenças Negligenciadas e Câncer. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Ciências Patológicas. Laboratório de Imunoparasitologia de Doenças Negligenciadas e Câncer. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Ciências Patológicas. Laboratório de Imunoparasitologia de Doenças Negligenciadas e Câncer. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Ciências Patológicas. Laboratório de Imunoparasitologia de Doenças Negligenciadas e Câncer. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Ciências Patológicas. Laboratório de Imunoparasitologia de Doenças Negligenciadas e Câncer. Londrina, PR, Brasil.American tegumentary leishmaniasis, a zoonotic disease caused by the Leishmania genus, poses significant challenges in treatment, including administration difficulty, low efficacy, and parasite resistance. Novel compounds or associations offer alternative therapies, and natural products such as oregano essential oil (OEO), extracted from Origanum vulgare, have been extensively researched due to biological effects, including antibacterial, antifungal, and antiparasitic properties. Silver nanoparticles (AgNp), a nanomaterial with compelling antimicrobial and antiparasitic activity, have been shown to exhibit potent leishmanicidal properties. We evaluated the in vitro effect of OEO and AgNp-Bio association on L. amazonensis and the death mechanisms of the parasite involved. Our results demonstrated a synergistic antileishmanial effect of OEO + AgNp on promastigote forms and L. amazonensis-infected macrophages, which induced morphological and ultrastructural changes in promastigotes. Subsequently, we investigated the mechanisms underlying parasite death and showed an increase in NO, ROS, mitochondrial depolarization, accumulation of lipid-storage bodies, autophagic vacuoles, phosphatidylserine exposure, and damage to the plasma membrane. Moreover, the association resulted in a reduction in the percentage of infected cells and the number of amastigotes per macrophage. In conclusion, our findings establish that OEO + AgNp elicits a late apoptosis-like mechanism to combat promastigote forms and promotes ROS and NO production in infected macrophages to target intracellular amastigote forms.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/59223/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALpathogens-12-00660OK.pdfpathogens-12-00660OK.pdfapplication/pdf3239344https://www.arca.fiocruz.br/bitstream/icict/59223/2/pathogens-12-00660OK.pdf31441cf215bfdc6cfde0e2a7ae74d2f3MD52icict/592232023-06-28 13:01:57.236oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-06-28T16:01:57Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.en_US.fl_str_mv Synergistic antileishmanial effect of oregano essential oil and silver nanoparticles: mechanisms of action on Leishmania amazonensis
title Synergistic antileishmanial effect of oregano essential oil and silver nanoparticles: mechanisms of action on Leishmania amazonensis
spellingShingle Synergistic antileishmanial effect of oregano essential oil and silver nanoparticles: mechanisms of action on Leishmania amazonensis
Alves, Alex Barbosa
Origanum
Leishmaniasis
Plant Oils
Apoptosis
Antileishmaniasis
Aceites de Plantas
Huiles végétales
Leishmaniose
Orégano (Planta)
Óleos de Plantas
Apoptose
Antileishmaniose
title_short Synergistic antileishmanial effect of oregano essential oil and silver nanoparticles: mechanisms of action on Leishmania amazonensis
title_full Synergistic antileishmanial effect of oregano essential oil and silver nanoparticles: mechanisms of action on Leishmania amazonensis
title_fullStr Synergistic antileishmanial effect of oregano essential oil and silver nanoparticles: mechanisms of action on Leishmania amazonensis
title_full_unstemmed Synergistic antileishmanial effect of oregano essential oil and silver nanoparticles: mechanisms of action on Leishmania amazonensis
title_sort Synergistic antileishmanial effect of oregano essential oil and silver nanoparticles: mechanisms of action on Leishmania amazonensis
author Alves, Alex Barbosa
author_facet Alves, Alex Barbosa
Bortoleti, Bruna Taciane da Silva
Tomiotto-Pellissier, Fernanda
Ganaza, Ana Flávia Marques
Gonçalves, Manoela Daiele
Carloto, Amanda Cristina Machado
Rodrigues, Ana Carolina Jacob
Silva, Taylon Felipe
Nakazato, Gerson
Kobayashi, Renata Katsuko Takayama
Lazarin-Bidóia, Danielle
Miranda-Sapla, Milena Menegazzo
Costa, Idessania Nazareth
Pavanelli, Wander Rogério
Conchon-Costa, Ivete
author_role author
author2 Bortoleti, Bruna Taciane da Silva
Tomiotto-Pellissier, Fernanda
Ganaza, Ana Flávia Marques
Gonçalves, Manoela Daiele
Carloto, Amanda Cristina Machado
Rodrigues, Ana Carolina Jacob
Silva, Taylon Felipe
Nakazato, Gerson
Kobayashi, Renata Katsuko Takayama
Lazarin-Bidóia, Danielle
Miranda-Sapla, Milena Menegazzo
Costa, Idessania Nazareth
Pavanelli, Wander Rogério
Conchon-Costa, Ivete
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Alves, Alex Barbosa
Bortoleti, Bruna Taciane da Silva
Tomiotto-Pellissier, Fernanda
Ganaza, Ana Flávia Marques
Gonçalves, Manoela Daiele
Carloto, Amanda Cristina Machado
Rodrigues, Ana Carolina Jacob
Silva, Taylon Felipe
Nakazato, Gerson
Kobayashi, Renata Katsuko Takayama
Lazarin-Bidóia, Danielle
Miranda-Sapla, Milena Menegazzo
Costa, Idessania Nazareth
Pavanelli, Wander Rogério
Conchon-Costa, Ivete
dc.subject.other.en_US.fl_str_mv Origanum
topic Origanum
Leishmaniasis
Plant Oils
Apoptosis
Antileishmaniasis
Aceites de Plantas
Huiles végétales
Leishmaniose
Orégano (Planta)
Óleos de Plantas
Apoptose
Antileishmaniose
dc.subject.en.en_US.fl_str_mv Leishmaniasis
Plant Oils
Apoptosis
Antileishmaniasis
dc.subject.es.en_US.fl_str_mv Aceites de Plantas
dc.subject.fr.en_US.fl_str_mv Huiles végétales
dc.subject.decs.en_US.fl_str_mv Leishmaniose
Orégano (Planta)
Óleos de Plantas
Apoptose
Antileishmaniose
description Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Ciências Patológicas. Laboratório de Imunoparasitologia de Doenças Negligenciadas e Câncer. Londrina, PR, Brasil.
publishDate 2023
dc.date.accessioned.fl_str_mv 2023-06-28T16:01:56Z
dc.date.available.fl_str_mv 2023-06-28T16:01:56Z
dc.date.issued.fl_str_mv 2023
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 ALVES, Alex Barbosa et al. Synergistic antileishmanial effect of oregano essential oil and silver nanoparticles: mechanisms of action on Leishmania amazonensis. Pathogens, v. 12, n. 660, p. 1-17, 2023.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/59223
dc.identifier.issn.en_US.fl_str_mv 2076-0817
dc.identifier.doi.none.fl_str_mv https://doi.org/10.3390/ pathogens12050660
identifier_str_mv ALVES, Alex Barbosa et al. Synergistic antileishmanial effect of oregano essential oil and silver nanoparticles: mechanisms of action on Leishmania amazonensis. Pathogens, v. 12, n. 660, p. 1-17, 2023.
2076-0817
url https://www.arca.fiocruz.br/handle/icict/59223
https://doi.org/10.3390/ pathogens12050660
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
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/59223/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/59223/2/pathogens-12-00660OK.pdf
bitstream.checksum.fl_str_mv 5a560609d32a3863062d77ff32785d58
31441cf215bfdc6cfde0e2a7ae74d2f3
bitstream.checksumAlgorithm.fl_str_mv 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_ 1798324729865568256