Atividade da punicalagina em leveduras do complexo Cryptococcus neoformans e de espécies de Candida
Ano de defesa: | 2017 |
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Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , , , , |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Goiás
|
Programa de Pós-Graduação: |
Programa de Pós-graduação em Medicina Tropical e Saúde Publica (IPTSP)
|
Departamento: |
Instituto de Patologia Tropical e Saúde Pública - IPTSP (RG)
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.bc.ufg.br/tede/handle/tede/8293 |
Resumo: | Introduction: the high incidence and mortality rate due to fungal infections arouse interest in the search for more effective and less toxic drugs for the treatment of these infections. Medicinal plants represent a promising source of discovery of antifungal agents. Among the medicinal plants, Lafoensia pacari A. St.-Hil (Lythraceae), plant of the cerrado, stands out for having medicinal properties popularly known in Brazil. Punicalagina, a secondary metabolite extracted from L. pacari leaf, has proven biological activities. Objective: in this work the biological activity of punicalagin on yeasts belonging to the Cryptococcus neoformans species complex and Candida species was evaluated. Methods: the in vitro susceptibility of the yeast to the compound punicalagin was verified using the broth microdilution method. The possible mechanism of action was verified by different methods such as: ergosterol assay of the fungal cell membrane, by morphological and ultrastructural analyzes of the yeasts, by flow cytometry (cell cycle, cytoplasmic membrane injury, reactive oxygen species production and loss of the mitochondrial membrane potential). The in vitro cytotoxicity of punicalagin was verified using Balb/c 3T3 cells, A549 lung carcinoma cells and sheep erythrocytes. Results: the punicalagin was able to inhibit yeast growth at concentrations ≤4 μg/mL with minimum fungicidal concentration (CFM) of >256 μg/mL. The punicalagin reduced the ergosterol synthesis of the fungal cell membrane and promoted alterations in the morphology and the cellular arrangement of the yeasts. The action mechanism analyzed by flow cytometry showed alteration of the cell cycle with increase of the G0/G1 phases and reduction of the G2/M phases, interfering in the cellular division of the DNA of the fungal cells. The compound showed low toxicity on the Balb/c cells 3T3, A549 and sheep erythrocytes. Conclusion: the results presented by punicalagin showed that this compound presents low cytotoxicity to the animal cells, with important antifungal activity against the yeasts of the Cryptococcus neoformans species complex and Candida species. |
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Silva, Maria do Rosário Rodrigueshttp://lattes.cnpq.br/7119226630434725Silva, Maria do Rosário RodriguesOliveira, Valéria deEspíndola, Laila SalmenCosta, Carolina RodriguesBara, Maria Teresa Freitashttp://lattes.cnpq.br/4862087796096790Silva, Thaísa Cristina2018-04-03T11:05:20Z2017-09-12SILVA, T. C. Atividade da punicalagina em leveduras do complexo Cryptococcus neoformans e de espécies de Candida. 2017. 109 f. Tese (Doutorado em Medicina Tropical e Saúde Pública) - Universidade Federal de Goiás, Goiânia, 2017.http://repositorio.bc.ufg.br/tede/handle/tede/8293Introduction: the high incidence and mortality rate due to fungal infections arouse interest in the search for more effective and less toxic drugs for the treatment of these infections. Medicinal plants represent a promising source of discovery of antifungal agents. Among the medicinal plants, Lafoensia pacari A. St.-Hil (Lythraceae), plant of the cerrado, stands out for having medicinal properties popularly known in Brazil. Punicalagina, a secondary metabolite extracted from L. pacari leaf, has proven biological activities. Objective: in this work the biological activity of punicalagin on yeasts belonging to the Cryptococcus neoformans species complex and Candida species was evaluated. Methods: the in vitro susceptibility of the yeast to the compound punicalagin was verified using the broth microdilution method. The possible mechanism of action was verified by different methods such as: ergosterol assay of the fungal cell membrane, by morphological and ultrastructural analyzes of the yeasts, by flow cytometry (cell cycle, cytoplasmic membrane injury, reactive oxygen species production and loss of the mitochondrial membrane potential). The in vitro cytotoxicity of punicalagin was verified using Balb/c 3T3 cells, A549 lung carcinoma cells and sheep erythrocytes. Results: the punicalagin was able to inhibit yeast growth at concentrations ≤4 μg/mL with minimum fungicidal concentration (CFM) of >256 μg/mL. The punicalagin reduced the ergosterol synthesis of the fungal cell membrane and promoted alterations in the morphology and the cellular arrangement of the yeasts. The action mechanism analyzed by flow cytometry showed alteration of the cell cycle with increase of the G0/G1 phases and reduction of the G2/M phases, interfering in the cellular division of the DNA of the fungal cells. The compound showed low toxicity on the Balb/c cells 3T3, A549 and sheep erythrocytes. Conclusion: the results presented by punicalagin showed that this compound presents low cytotoxicity to the animal cells, with important antifungal activity against the yeasts of the Cryptococcus neoformans species complex and Candida species.Introdução: a elevada incidência e taxa de mortalidade por infecções fúngicas despertam o interesse pela busca por fármacos mais eficazes e menos tóxicos para o tratamento dessas infecções. Plantas medicinais representam uma promissora fonte de descoberta de agentes antifúngicos. Dentre as plantas medicinais, a Lafoensia pacari A. St.-Hil (Lythraceae), planta do cerrado, destaca-se por apresentar propriedades medicinais conhecidas popularmente no Brasil. A punicalagina, um metabólito secundário extraído da folha da L. pacari, apresenta comprovadas atividades biológicas. Objetivo: neste trabalho foi avaliada a atividade biológica de punicalagina sobre leveduras pertencentes ao complexo Cryptococcus neoformans e espécies de Candida. Métodos: a suscetibilidade in vitro das leveduras ao composto punicalagina, foi verificada usando-se o método de microdiluição em caldo. O possível mecanismo de ação foi verificado por diferentes métodos como: doseamento de ergosterol da membrana da célula fúngica, por análises morfológicas e ultraestruturais das leveduras, por citometria de fluxo (ciclo celular, lesão da membrana citoplasmática, produção de espécies reativas de oxigênio e perda do potencial da membrana mitocondrial). A citotoxicidade in vitro de punicalagina foi verificada utilizando-se células Balb/c 3T3, células de carcinoma pulmonar A549 e eritrócitos de carneiro. Resultados: a punicalagina foi capaz de inibir o crescimento das leveduras em concentrações ≤ 4 µg/mL com concentração fungicida mínima (CFM) de > 256 µg/mL. A punicalagina reduziu a síntese de ergosterol da membrana celular fúngica e promoveu alterações na morfologia e no arranjo celular das leveduras. O mecanismo de ação analisado por citometria de fluxo mostrou alteração do ciclo celular com aumento das fases G0/G1 e redução das fases G2/M, interferindo na divisão celular do DNA das células fúngicas. O composto mostrou baixa toxicidade sobre as células Balb/c 3T3, A549 e eritrócitos de carneiro. Conclusão: os resultados apresentados pela ação da punicalagina mostraram que este composto apresenta baixa citotoxicidade para as células animais, com importante atividade antifúngica para as leveduras do complexo Cryptococcus neoformans e Candida.Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2018-04-03T11:03:00Z No. of bitstreams: 2 Tese - Thaísa Cristina Silva - 2017.pdf: 8533061 bytes, checksum: 987601f85d9b8f33eb97a24c3e474df3 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2018-04-03T11:05:20Z (GMT) No. of bitstreams: 2 Tese - Thaísa Cristina Silva - 2017.pdf: 8533061 bytes, checksum: 987601f85d9b8f33eb97a24c3e474df3 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Made available in DSpace on 2018-04-03T11:05:20Z (GMT). No. of bitstreams: 2 Tese - Thaísa Cristina Silva - 2017.pdf: 8533061 bytes, checksum: 987601f85d9b8f33eb97a24c3e474df3 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-09-12Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESapplication/pdfporUniversidade Federal de GoiásPrograma de Pós-graduação em Medicina Tropical e Saúde Publica (IPTSP)UFGBrasilInstituto de Patologia Tropical e Saúde Pública - IPTSP (RG)http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessPunicalaginaAtividade antifúngicaCandidaCryptococcus neoformansPunicalaginAntifungal activityCandidaCryptococcus neoformansMICROBIOLOGIA APLICADA::MICROBIOLOGIA MEDICAAtividade da punicalagina em leveduras do complexo Cryptococcus neoformans e de espécies de CandidaActivity of punicalagin in yeasts of the complex Cryptococcus neoformans and Candida speciesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesis6085308344741430434600600600600-776901144456455628886481875776613505852075167498588264571reponame:Repositório Institucional da UFGinstname:Universidade Federal de Goiás (UFG)instacron:UFGLICENSElicense.txtlicense.txttext/plain; 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dc.title.eng.fl_str_mv |
Atividade da punicalagina em leveduras do complexo Cryptococcus neoformans e de espécies de Candida |
dc.title.alternative.eng.fl_str_mv |
Activity of punicalagin in yeasts of the complex Cryptococcus neoformans and Candida species |
title |
Atividade da punicalagina em leveduras do complexo Cryptococcus neoformans e de espécies de Candida |
spellingShingle |
Atividade da punicalagina em leveduras do complexo Cryptococcus neoformans e de espécies de Candida Silva, Thaísa Cristina Punicalagina Atividade antifúngica Candida Cryptococcus neoformans Punicalagin Antifungal activity Candida Cryptococcus neoformans MICROBIOLOGIA APLICADA::MICROBIOLOGIA MEDICA |
title_short |
Atividade da punicalagina em leveduras do complexo Cryptococcus neoformans e de espécies de Candida |
title_full |
Atividade da punicalagina em leveduras do complexo Cryptococcus neoformans e de espécies de Candida |
title_fullStr |
Atividade da punicalagina em leveduras do complexo Cryptococcus neoformans e de espécies de Candida |
title_full_unstemmed |
Atividade da punicalagina em leveduras do complexo Cryptococcus neoformans e de espécies de Candida |
title_sort |
Atividade da punicalagina em leveduras do complexo Cryptococcus neoformans e de espécies de Candida |
author |
Silva, Thaísa Cristina |
author_facet |
Silva, Thaísa Cristina |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Silva, Maria do Rosário Rodrigues |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/7119226630434725 |
dc.contributor.referee1.fl_str_mv |
Silva, Maria do Rosário Rodrigues |
dc.contributor.referee2.fl_str_mv |
Oliveira, Valéria de |
dc.contributor.referee3.fl_str_mv |
Espíndola, Laila Salmen |
dc.contributor.referee4.fl_str_mv |
Costa, Carolina Rodrigues |
dc.contributor.referee5.fl_str_mv |
Bara, Maria Teresa Freitas |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/4862087796096790 |
dc.contributor.author.fl_str_mv |
Silva, Thaísa Cristina |
contributor_str_mv |
Silva, Maria do Rosário Rodrigues Silva, Maria do Rosário Rodrigues Oliveira, Valéria de Espíndola, Laila Salmen Costa, Carolina Rodrigues Bara, Maria Teresa Freitas |
dc.subject.por.fl_str_mv |
Punicalagina Atividade antifúngica Candida Cryptococcus neoformans |
topic |
Punicalagina Atividade antifúngica Candida Cryptococcus neoformans Punicalagin Antifungal activity Candida Cryptococcus neoformans MICROBIOLOGIA APLICADA::MICROBIOLOGIA MEDICA |
dc.subject.eng.fl_str_mv |
Punicalagin Antifungal activity Candida Cryptococcus neoformans |
dc.subject.cnpq.fl_str_mv |
MICROBIOLOGIA APLICADA::MICROBIOLOGIA MEDICA |
description |
Introduction: the high incidence and mortality rate due to fungal infections arouse interest in the search for more effective and less toxic drugs for the treatment of these infections. Medicinal plants represent a promising source of discovery of antifungal agents. Among the medicinal plants, Lafoensia pacari A. St.-Hil (Lythraceae), plant of the cerrado, stands out for having medicinal properties popularly known in Brazil. Punicalagina, a secondary metabolite extracted from L. pacari leaf, has proven biological activities. Objective: in this work the biological activity of punicalagin on yeasts belonging to the Cryptococcus neoformans species complex and Candida species was evaluated. Methods: the in vitro susceptibility of the yeast to the compound punicalagin was verified using the broth microdilution method. The possible mechanism of action was verified by different methods such as: ergosterol assay of the fungal cell membrane, by morphological and ultrastructural analyzes of the yeasts, by flow cytometry (cell cycle, cytoplasmic membrane injury, reactive oxygen species production and loss of the mitochondrial membrane potential). The in vitro cytotoxicity of punicalagin was verified using Balb/c 3T3 cells, A549 lung carcinoma cells and sheep erythrocytes. Results: the punicalagin was able to inhibit yeast growth at concentrations ≤4 μg/mL with minimum fungicidal concentration (CFM) of >256 μg/mL. The punicalagin reduced the ergosterol synthesis of the fungal cell membrane and promoted alterations in the morphology and the cellular arrangement of the yeasts. The action mechanism analyzed by flow cytometry showed alteration of the cell cycle with increase of the G0/G1 phases and reduction of the G2/M phases, interfering in the cellular division of the DNA of the fungal cells. The compound showed low toxicity on the Balb/c cells 3T3, A549 and sheep erythrocytes. Conclusion: the results presented by punicalagin showed that this compound presents low cytotoxicity to the animal cells, with important antifungal activity against the yeasts of the Cryptococcus neoformans species complex and Candida species. |
publishDate |
2017 |
dc.date.issued.fl_str_mv |
2017-09-12 |
dc.date.accessioned.fl_str_mv |
2018-04-03T11:05:20Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
SILVA, T. C. Atividade da punicalagina em leveduras do complexo Cryptococcus neoformans e de espécies de Candida. 2017. 109 f. Tese (Doutorado em Medicina Tropical e Saúde Pública) - Universidade Federal de Goiás, Goiânia, 2017. |
dc.identifier.uri.fl_str_mv |
http://repositorio.bc.ufg.br/tede/handle/tede/8293 |
identifier_str_mv |
SILVA, T. C. Atividade da punicalagina em leveduras do complexo Cryptococcus neoformans e de espécies de Candida. 2017. 109 f. Tese (Doutorado em Medicina Tropical e Saúde Pública) - Universidade Federal de Goiás, Goiânia, 2017. |
url |
http://repositorio.bc.ufg.br/tede/handle/tede/8293 |
dc.language.iso.fl_str_mv |
por |
language |
por |
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6085308344741430434 |
dc.relation.confidence.fl_str_mv |
600 600 600 600 |
dc.relation.department.fl_str_mv |
-7769011444564556288 |
dc.relation.cnpq.fl_str_mv |
8648187577661350585 |
dc.relation.sponsorship.fl_str_mv |
2075167498588264571 |
dc.rights.driver.fl_str_mv |
http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Goiás |
dc.publisher.program.fl_str_mv |
Programa de Pós-graduação em Medicina Tropical e Saúde Publica (IPTSP) |
dc.publisher.initials.fl_str_mv |
UFG |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Instituto de Patologia Tropical e Saúde Pública - IPTSP (RG) |
publisher.none.fl_str_mv |
Universidade Federal de Goiás |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFG instname:Universidade Federal de Goiás (UFG) instacron:UFG |
instname_str |
Universidade Federal de Goiás (UFG) |
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UFG |
institution |
UFG |
reponame_str |
Repositório Institucional da UFG |
collection |
Repositório Institucional da UFG |
bitstream.url.fl_str_mv |
http://repositorio.bc.ufg.br/tede/bitstreams/85919d4a-3206-4193-bbfc-b3a52443d136/download http://repositorio.bc.ufg.br/tede/bitstreams/88f4e4c0-6451-4289-afe2-98d5a9e7bb5c/download http://repositorio.bc.ufg.br/tede/bitstreams/f5abc295-d6e2-40a8-a65d-d3e5952ae3ca/download http://repositorio.bc.ufg.br/tede/bitstreams/d9940073-0a4b-4ee8-81bc-5c543e7b68e8/download http://repositorio.bc.ufg.br/tede/bitstreams/bdcb9bf6-2c95-4879-ab9f-47180e0c061e/download |
bitstream.checksum.fl_str_mv |
bd3efa91386c1718a7f26a329fdcb468 4afdbb8c545fd630ea7db775da747b2f d41d8cd98f00b204e9800998ecf8427e d41d8cd98f00b204e9800998ecf8427e 987601f85d9b8f33eb97a24c3e474df3 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional da UFG - Universidade Federal de Goiás (UFG) |
repository.mail.fl_str_mv |
tasesdissertacoes.bc@ufg.br |
_version_ |
1798044963608461312 |