Carajurin Induces Apoptosis in Leishmania amazonensis Promastigotes through Reactive Oxygen Species Production and Mitochondrial Dysfunction
| Autor(a) principal: | |
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| Data de Publicação: | 2022 |
| 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/53601 |
Resumo: | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil. |
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Silva, João Victor SilvaMoragas-Tellis, Carla J. Moragas-TellisChagas, Maria S. S.Souza, Paulo Victor R.Moreira, Davyson L.Hardoim, Daiana J.Taniwaki, Noemi N.Costa, Vanessa F. A.Bertho, Alvaro L.Brondani, DanielaZapp, EduardoOliveira, Aldo Sena deCalabrese, Kátia S.Behrens, Maria D.Souza, Fernando Almeida2022-06-30T19:36:54Z2022-06-30T19:36:54Z2022SILVA, João Victor Silva et al. Carajurin Induces Apoptosis in Leishmania amazonensis Promastigotes through Reactive Oxygen Species Production and Mitochondrial Dysfunction. Pharmaceuticals, v. 15, 331, p. 1 - 18, Mar. 2022.1999-4923https://www.arca.fiocruz.br/handle/icict/5360110.3390/ ph15030331engMDPILeishmania amazonensisLeishmania amazonensisMitocôndriaMorte celularApoptoseCarajurinLeishmania amazonensisMitochondriaCell deathApoptosisCarajurin Induces Apoptosis in Leishmania amazonensis Promastigotes through Reactive Oxygen Species Production and Mitochondrial Dysfunctioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia Farmacêutica, Farmanguinhos. Laboratório de Produtos Naturais para Saúde Pública. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia Farmacêutica, Farmanguinhos. Laboratório de Produtos Naturais para Saúde Pública. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia Farmacêutica, Farmanguinhos. Laboratório de Produtos Naturais para Saúde Pública. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto de Tecnologia Farmacêutica, Farmanguinhos. Programa de Pós-Graduação em Pesquisa Translacional em Drogas e Medicamentos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia Farmacêutica, Farmanguinhos. Laboratório de Produtos Naturais para Saúde Pública. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil.Instituto Adolfo Lutz. Núcleo de Microscopia Eletrônica. São Paulo, SP,. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Plataforma Tecnológica de Citometria de Fluxo. Rio de Janeiro, RJ, Brasil.Universidade Federal de Santa Catarina. Departamento de Ciências Exatas e Educação. Grupo de Pesquisa em Química Medicinal e Biológica. Blumenau, SC, Brasil.Universidade Federal de Santa Catarina. Departamento de Ciências Exatas e Educação. Grupo de Pesquisa em Química Medicinal e Biológica. Blumenau, SC, Brasil.Universidade Federal de Santa Catarina. Departamento de Ciências Exatas e Educação. Grupo de Pesquisa em Química Medicinal e Biológica. Blumenau, SC, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil..Fundação Oswaldo Cruz. Instituto de Tecnologia Farmacêutica, Farmanguinhos. Laboratório de Produtos Naturais para Saúde Pública. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil / Universidade Estadual do Maranhão. Programa de Pós-Graduação em Ciência Animal. São Luis, MA, Brasil.Carajurin is the main constituent of Arrabidaea chica species with reported anti-Leishmania activity. However, its mechanism of action has not been described. This study investigated the mechanisms of action of carajurin against promastigote forms of Leishmania amazonensis. Carajurin was effective against promastigotes with IC50 of 7.96 1.23 g.mL1 (26.4 M), and the cytotoxic concentration for peritoneal macrophages was 258.2 1.20 g.mL1 (856.9 M) after 24 h of treatment. Ultrastructural evaluation highlighted pronounced swelling of the kinetoplast with loss of electron-density in L. amazonensis promastigotes induced by carajurin treatment. It was observed that carajurin leads to a decrease in the mitochondrial membrane potential (p = 0.0286), an increase in reactive oxygen species production (p = 0.0286), and cell death by late apoptosis (p = 0.0095) in parasites. Pretreatment with the antioxidant NAC prevented ROS production and significantly reduced carajurin-induced cell death. The electrochemical and density functional theory (DFT) data contributed to support the molecular mechanism of action of carajurin associated with the ROS generation, for which it is possible to observe a correlation between the LUMO energy and the electroactivity of carajurin in the presence of molecular oxygen. All these results suggest that carajurin targets the mitochondria in L. amazonensis. In addition, when assessed for its drug-likeness, carajurin follows Lipinski”s rule of five, and the Ghose, Veber, Egan, and Muegge criteria.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/53601/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALJoaoVitorSilva_AlvaroBertho_etal_IOC_2022.pdfJoaoVitorSilva_AlvaroBertho_etal_IOC_2022.pdfapplication/pdf4263743https://www.arca.fiocruz.br/bitstream/icict/53601/2/JoaoVitorSilva_AlvaroBertho_etal_IOC_2022.pdffcd6e8ae241374e83d5a752ab0cddcbdMD52icict/536012022-06-30 16:36:54.124oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352022-06-30T19:36:54Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
| dc.title.pt_BR.fl_str_mv |
Carajurin Induces Apoptosis in Leishmania amazonensis Promastigotes through Reactive Oxygen Species Production and Mitochondrial Dysfunction |
| title |
Carajurin Induces Apoptosis in Leishmania amazonensis Promastigotes through Reactive Oxygen Species Production and Mitochondrial Dysfunction |
| spellingShingle |
Carajurin Induces Apoptosis in Leishmania amazonensis Promastigotes through Reactive Oxygen Species Production and Mitochondrial Dysfunction Silva, João Victor Silva Leishmania amazonensis Leishmania amazonensis Mitocôndria Morte celular Apoptose Carajurin Leishmania amazonensis Mitochondria Cell death Apoptosis |
| title_short |
Carajurin Induces Apoptosis in Leishmania amazonensis Promastigotes through Reactive Oxygen Species Production and Mitochondrial Dysfunction |
| title_full |
Carajurin Induces Apoptosis in Leishmania amazonensis Promastigotes through Reactive Oxygen Species Production and Mitochondrial Dysfunction |
| title_fullStr |
Carajurin Induces Apoptosis in Leishmania amazonensis Promastigotes through Reactive Oxygen Species Production and Mitochondrial Dysfunction |
| title_full_unstemmed |
Carajurin Induces Apoptosis in Leishmania amazonensis Promastigotes through Reactive Oxygen Species Production and Mitochondrial Dysfunction |
| title_sort |
Carajurin Induces Apoptosis in Leishmania amazonensis Promastigotes through Reactive Oxygen Species Production and Mitochondrial Dysfunction |
| author |
Silva, João Victor Silva |
| author_facet |
Silva, João Victor Silva Moragas-Tellis, Carla J. Moragas-Tellis Chagas, Maria S. S. Souza, Paulo Victor R. Moreira, Davyson L. Hardoim, Daiana J. Taniwaki, Noemi N. Costa, Vanessa F. A. Bertho, Alvaro L. Brondani, Daniela Zapp, Eduardo Oliveira, Aldo Sena de Calabrese, Kátia S. Behrens, Maria D. Souza, Fernando Almeida |
| author_role |
author |
| author2 |
Moragas-Tellis, Carla J. Moragas-Tellis Chagas, Maria S. S. Souza, Paulo Victor R. Moreira, Davyson L. Hardoim, Daiana J. Taniwaki, Noemi N. Costa, Vanessa F. A. Bertho, Alvaro L. Brondani, Daniela Zapp, Eduardo Oliveira, Aldo Sena de Calabrese, Kátia S. Behrens, Maria D. Souza, Fernando Almeida |
| author2_role |
author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Silva, João Victor Silva Moragas-Tellis, Carla J. Moragas-Tellis Chagas, Maria S. S. Souza, Paulo Victor R. Moreira, Davyson L. Hardoim, Daiana J. Taniwaki, Noemi N. Costa, Vanessa F. A. Bertho, Alvaro L. Brondani, Daniela Zapp, Eduardo Oliveira, Aldo Sena de Calabrese, Kátia S. Behrens, Maria D. Souza, Fernando Almeida |
| dc.subject.other.pt_BR.fl_str_mv |
Leishmania amazonensis Leishmania amazonensis Mitocôndria Morte celular Apoptose |
| topic |
Leishmania amazonensis Leishmania amazonensis Mitocôndria Morte celular Apoptose Carajurin Leishmania amazonensis Mitochondria Cell death Apoptosis |
| dc.subject.en.pt_BR.fl_str_mv |
Carajurin Leishmania amazonensis Mitochondria Cell death Apoptosis |
| description |
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil. |
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2022 |
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2022-06-30T19:36:54Z |
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2022-06-30T19:36:54Z |
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2022 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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SILVA, João Victor Silva et al. Carajurin Induces Apoptosis in Leishmania amazonensis Promastigotes through Reactive Oxygen Species Production and Mitochondrial Dysfunction. Pharmaceuticals, v. 15, 331, p. 1 - 18, Mar. 2022. |
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https://www.arca.fiocruz.br/handle/icict/53601 |
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1999-4923 |
| dc.identifier.doi.none.fl_str_mv |
10.3390/ ph15030331 |
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SILVA, João Victor Silva et al. Carajurin Induces Apoptosis in Leishmania amazonensis Promastigotes through Reactive Oxygen Species Production and Mitochondrial Dysfunction. Pharmaceuticals, v. 15, 331, p. 1 - 18, Mar. 2022. 1999-4923 10.3390/ ph15030331 |
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