Suscetibilidade in vitro a antifúngicos, frações de óleos essenciais e modelo experimental de infecção por Malassezia pachydermatis
Ano de defesa: | 2018 |
---|---|
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 Santa Maria
Centro de Ciências da Saúde |
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Farmacologia
|
Departamento: |
Farmacologia
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/18687 |
Resumo: | Malassezia pachydermatis is a zoophilic yeast mainly found in the auditory canal of various animal species, and may also be isolated from the skin of humans. Azole and polyene antifungals are the treatment of choice for skin infections, related to Malassezia. However, studies have demonstrated the occurrence of resistance or lower susceptibility of this yeast to some drugs. In this context, the objective of this study was to evaluate the in vitro combination of antifungal agents and antifungals and essential oils fractions (EOs), based on the M27-A3 protocol, with modifications by the checkerboard method. In addition, we sought to evaluate the cytotoxic effects of carvacrol (CRV), cinnamaldehyde (CIN) and thymol (THY) in mouse fibroblasts (3T3 cell line) and to develop an experimental infection model in mice for M. pachydermatis. Combinations of antifungals showed a predominance of indifferent results, with the highest synergism rates for combinations of itraconazole+ caspofungin and clotrimazole+caspofungin (55.17%). Combinations of antifungal and OE fractions showed 80% synergistic interactions for combinations of CRV+nystatin, THY+ nystatin and CRV+miconazole. In cytotoxicity tests using MTT (β- (4,5-dimethylthiazol-2yl) -2,5-diphenyl tetrazoline bromide) CRV and THY were not cytotoxic at most of the concentrations tested (1-50μg/mL ), but CIN reduced cell viability at all concentrations There was a decrease in the concentrations of reactive oxygen species in the presence of CRV, CIN and THY at 24 and 72h, but an increase of 50μg/ml of CIN in 24h of incubation. An increase in DNA fragmentation levels at concentrations of 50 and 100μg/mL of CRV, 25-100μg/mL of CIN and at most THY concentrations was observed. an increase (up to 5%) in apoptosis after exposure to CRV and THY (25-50μg/mL) in 24-72h and an increase in the level of late apoptosis (up to 90%) with CIN (25μg/mL) in 24-72h An infection pattern for M. pachydermatis in Swiss mice immunocompromised with cyclophosphamide (CYP) and acetate hidrocortisone (HCA). This immunosuppressive protocol is already used in several studies to facilitate experimental fungal infections. Previous immunosuppression of the mice allowed infection of the dermis and ear of all animals. In addition, histopathological findings showed yeast, inflammation and hyperkeratosis, confirming otitis and dermatitis by M. pachydermatis. The results of the present study showed some combinations with high percentages of synergism, which allow the elaboration of new treatment hypotheses and point out some candidate combinations to be evaluated in experimental models in vivo. |
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2019-10-25T21:21:09Z2019-10-25T21:21:09Z2018-07-19http://repositorio.ufsm.br/handle/1/18687Malassezia pachydermatis is a zoophilic yeast mainly found in the auditory canal of various animal species, and may also be isolated from the skin of humans. Azole and polyene antifungals are the treatment of choice for skin infections, related to Malassezia. However, studies have demonstrated the occurrence of resistance or lower susceptibility of this yeast to some drugs. In this context, the objective of this study was to evaluate the in vitro combination of antifungal agents and antifungals and essential oils fractions (EOs), based on the M27-A3 protocol, with modifications by the checkerboard method. In addition, we sought to evaluate the cytotoxic effects of carvacrol (CRV), cinnamaldehyde (CIN) and thymol (THY) in mouse fibroblasts (3T3 cell line) and to develop an experimental infection model in mice for M. pachydermatis. Combinations of antifungals showed a predominance of indifferent results, with the highest synergism rates for combinations of itraconazole+ caspofungin and clotrimazole+caspofungin (55.17%). Combinations of antifungal and OE fractions showed 80% synergistic interactions for combinations of CRV+nystatin, THY+ nystatin and CRV+miconazole. In cytotoxicity tests using MTT (β- (4,5-dimethylthiazol-2yl) -2,5-diphenyl tetrazoline bromide) CRV and THY were not cytotoxic at most of the concentrations tested (1-50μg/mL ), but CIN reduced cell viability at all concentrations There was a decrease in the concentrations of reactive oxygen species in the presence of CRV, CIN and THY at 24 and 72h, but an increase of 50μg/ml of CIN in 24h of incubation. An increase in DNA fragmentation levels at concentrations of 50 and 100μg/mL of CRV, 25-100μg/mL of CIN and at most THY concentrations was observed. an increase (up to 5%) in apoptosis after exposure to CRV and THY (25-50μg/mL) in 24-72h and an increase in the level of late apoptosis (up to 90%) with CIN (25μg/mL) in 24-72h An infection pattern for M. pachydermatis in Swiss mice immunocompromised with cyclophosphamide (CYP) and acetate hidrocortisone (HCA). This immunosuppressive protocol is already used in several studies to facilitate experimental fungal infections. Previous immunosuppression of the mice allowed infection of the dermis and ear of all animals. In addition, histopathological findings showed yeast, inflammation and hyperkeratosis, confirming otitis and dermatitis by M. pachydermatis. The results of the present study showed some combinations with high percentages of synergism, which allow the elaboration of new treatment hypotheses and point out some candidate combinations to be evaluated in experimental models in vivo.Malassezia pachydermatis é uma levedura zoofílica encontrada principalmente no conduto auditivo de várias espécies de animais, podendo, também, ser isolada da pele de seres humanos. Antifúngicos azólicos e poliênicos são o tratamento de escolha para infecções de pele, relacionadas à Malassezia. No entanto, estudos têm demonstrado à ocorrência de resistência ou menor suscetibilidade desta levedura à algumas drogas. Neste contexto, este estudo teve como objetivos: avaliar a combinação in vitro de antifúngicos entre si e antifúngicos e frações de óleos essenciais (OEs), com base no protocolo M27-A3, com modificações, pelo método de “checkerboard”. Em adição buscou-se avaliar os efeitos citotóxicos do carvacrol (CRV), cinamaldeído (CIN) e timol (THY) em fibroblastos de camundongos (linhagem celular 3T3) e desenvolver um modelo de infecção experimental em camundongos para M. pachydermatis. As combinações entre antifúngicos apresentaram um predomínio de resultados indiferentes, com as maiores taxas de sinergismo para as combinações de itraconazol+caspofungina e clotrimazol+caspofungina (55,17%). As combinações de antifúngicos e frações de OEs apresentaram 80% de interações sinérgicas para as combinações de CRV + nistatina, THY + nistatina e CRV + miconazol. Nos testes de citotoxicidade utilizando o MTT ((3-(4,5-dimetiltiazol-2yl)-2,5-difenil brometo de tetrazolina) CRV e THY não mostraram-se citotóxicos na maioria das concentrações testadas (1-50 μg / mL), mas o CIN reduziu a viabilidade celular em todas as concentrações. Houve uma diminuição nas concentrações de espécies reativas de oxigênio na presença de CRV, CIN e THY em 24 e 72 h, mas observou-se um aumento na concentração de 50 μg / mL de CIN em 24 h de incubação. Foi observado um aumento nos níveis de fragmentação do DNA nas concentrações de 50 e 100 μg / mL de CRV, 25-100 μg / mL de CIN e na maioria das concentrações de THY. Observou-se um aumento (até 5%) na apoptose após exposição a CRV e THY (25-50 μg / mL) em 24-72 h e um aumento no nível de apoptose tardia (até 90%) com CIN (25 μg / mL) em 24-72 h. Foi desenvolvido um modelo de infecção para M. pachydermatis em camundongos Swiss imunocomprometidos com ciclofosfamida (CYP) e acetato de hidrocortisona (HCA). Esse protocolo de imunossupressão já é usado em diversos estudos para facilitar infecções fúngicas experimentais. A imunossupressão prévia dos camundongos permitiu a infecção da derme e da orelha de todos os animais. Além disso, os achados histopatológicos mostraram leveduras, inflamação e hiperqueratose, confirmando otite e dermatite por M. pachydermatis. Os resultados do presente estudo mostraram algumas combinações com altos percentuais de sinergismo, as quais, permitem a elaboração de novas hipóteses de tratamento e apontam algumas combinações candidatas a serem avaliadas em modelos experimentais in vivo.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade Federal de Santa MariaCentro de Ciências da SaúdePrograma de Pós-Graduação em FarmacologiaUFSMBrasilFarmacologiaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessMalassezia pachydermatisSuscetibilidadeAntifúngicosÓleos essenciaisModelo de infecçãoSusceptibilitySusceptibilityAntifungalsEssencial oilsModel of infectionCNPQ::CIENCIAS DA SAUDE::FARMACIASuscetibilidade in vitro a antifúngicos, frações de óleos essenciais e modelo experimental de infecção por Malassezia pachydermatisIn vitro suscetibility to antifungals, fractions of essential oils and experimental model of infection by Malassezia pachydermatisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisSanturio, Janio Moraishttp://lattes.cnpq.br/6316012260769979Alves, Sydney Hartzhttp://lattes.cnpq.br/0330782478769631Botton, Sônia de Avilahttp://lattes.cnpq.br/0814772095155945Loreto, Érico Silva dehttp://lattes.cnpq.br/5475233864057995Denardi, Laura Bedinhttp://lattes.cnpq.br/0673126998191701http://lattes.cnpq.br/2330632247520007Schlemmer, Karine Bizzi40030000000560006a1b29c-fde0-4a69-8097-2a9d6a9d964986be3930-0495-4583-b4ce-11d61591fd607928080e-16be-47fd-b0a3-6d394fcd82a7860bd8db-e3f1-4b8e-bb3e-f1c8f0b143064873446f-c73b-4a20-a09a-7bdd83da9aedf7863681-fc05-4ab4-a062-3b588f2b3ffareponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALTES_PPGFARMACOLOGIA_2018_SCHLEMMER_KARINE.pdfTES_PPGFARMACOLOGIA_2018_SCHLEMMER_KARINE.pdfTese de Doutoradoapplication/pdf2606683http://repositorio.ufsm.br/bitstream/1/18687/1/TES_PPGFARMACOLOGIA_2018_SCHLEMMER_KARINE.pdf6c4cc227d12acd9d036b7b8f541d78feMD51LICENSElicense.txtlicense.txttext/plain; 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dc.title.por.fl_str_mv |
Suscetibilidade in vitro a antifúngicos, frações de óleos essenciais e modelo experimental de infecção por Malassezia pachydermatis |
dc.title.alternative.eng.fl_str_mv |
In vitro suscetibility to antifungals, fractions of essential oils and experimental model of infection by Malassezia pachydermatis |
title |
Suscetibilidade in vitro a antifúngicos, frações de óleos essenciais e modelo experimental de infecção por Malassezia pachydermatis |
spellingShingle |
Suscetibilidade in vitro a antifúngicos, frações de óleos essenciais e modelo experimental de infecção por Malassezia pachydermatis Schlemmer, Karine Bizzi Malassezia pachydermatis Suscetibilidade Antifúngicos Óleos essenciais Modelo de infecção Susceptibility Susceptibility Antifungals Essencial oils Model of infection CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Suscetibilidade in vitro a antifúngicos, frações de óleos essenciais e modelo experimental de infecção por Malassezia pachydermatis |
title_full |
Suscetibilidade in vitro a antifúngicos, frações de óleos essenciais e modelo experimental de infecção por Malassezia pachydermatis |
title_fullStr |
Suscetibilidade in vitro a antifúngicos, frações de óleos essenciais e modelo experimental de infecção por Malassezia pachydermatis |
title_full_unstemmed |
Suscetibilidade in vitro a antifúngicos, frações de óleos essenciais e modelo experimental de infecção por Malassezia pachydermatis |
title_sort |
Suscetibilidade in vitro a antifúngicos, frações de óleos essenciais e modelo experimental de infecção por Malassezia pachydermatis |
author |
Schlemmer, Karine Bizzi |
author_facet |
Schlemmer, Karine Bizzi |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Santurio, Janio Morais |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/6316012260769979 |
dc.contributor.referee1.fl_str_mv |
Alves, Sydney Hartz |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/0330782478769631 |
dc.contributor.referee2.fl_str_mv |
Botton, Sônia de Avila |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/0814772095155945 |
dc.contributor.referee3.fl_str_mv |
Loreto, Érico Silva de |
dc.contributor.referee3Lattes.fl_str_mv |
http://lattes.cnpq.br/5475233864057995 |
dc.contributor.referee4.fl_str_mv |
Denardi, Laura Bedin |
dc.contributor.referee4Lattes.fl_str_mv |
http://lattes.cnpq.br/0673126998191701 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/2330632247520007 |
dc.contributor.author.fl_str_mv |
Schlemmer, Karine Bizzi |
contributor_str_mv |
Santurio, Janio Morais Alves, Sydney Hartz Botton, Sônia de Avila Loreto, Érico Silva de Denardi, Laura Bedin |
dc.subject.por.fl_str_mv |
Malassezia pachydermatis Suscetibilidade Antifúngicos Óleos essenciais Modelo de infecção |
topic |
Malassezia pachydermatis Suscetibilidade Antifúngicos Óleos essenciais Modelo de infecção Susceptibility Susceptibility Antifungals Essencial oils Model of infection CNPQ::CIENCIAS DA SAUDE::FARMACIA |
dc.subject.eng.fl_str_mv |
Susceptibility Susceptibility Antifungals Essencial oils Model of infection |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
Malassezia pachydermatis is a zoophilic yeast mainly found in the auditory canal of various animal species, and may also be isolated from the skin of humans. Azole and polyene antifungals are the treatment of choice for skin infections, related to Malassezia. However, studies have demonstrated the occurrence of resistance or lower susceptibility of this yeast to some drugs. In this context, the objective of this study was to evaluate the in vitro combination of antifungal agents and antifungals and essential oils fractions (EOs), based on the M27-A3 protocol, with modifications by the checkerboard method. In addition, we sought to evaluate the cytotoxic effects of carvacrol (CRV), cinnamaldehyde (CIN) and thymol (THY) in mouse fibroblasts (3T3 cell line) and to develop an experimental infection model in mice for M. pachydermatis. Combinations of antifungals showed a predominance of indifferent results, with the highest synergism rates for combinations of itraconazole+ caspofungin and clotrimazole+caspofungin (55.17%). Combinations of antifungal and OE fractions showed 80% synergistic interactions for combinations of CRV+nystatin, THY+ nystatin and CRV+miconazole. In cytotoxicity tests using MTT (β- (4,5-dimethylthiazol-2yl) -2,5-diphenyl tetrazoline bromide) CRV and THY were not cytotoxic at most of the concentrations tested (1-50μg/mL ), but CIN reduced cell viability at all concentrations There was a decrease in the concentrations of reactive oxygen species in the presence of CRV, CIN and THY at 24 and 72h, but an increase of 50μg/ml of CIN in 24h of incubation. An increase in DNA fragmentation levels at concentrations of 50 and 100μg/mL of CRV, 25-100μg/mL of CIN and at most THY concentrations was observed. an increase (up to 5%) in apoptosis after exposure to CRV and THY (25-50μg/mL) in 24-72h and an increase in the level of late apoptosis (up to 90%) with CIN (25μg/mL) in 24-72h An infection pattern for M. pachydermatis in Swiss mice immunocompromised with cyclophosphamide (CYP) and acetate hidrocortisone (HCA). This immunosuppressive protocol is already used in several studies to facilitate experimental fungal infections. Previous immunosuppression of the mice allowed infection of the dermis and ear of all animals. In addition, histopathological findings showed yeast, inflammation and hyperkeratosis, confirming otitis and dermatitis by M. pachydermatis. The results of the present study showed some combinations with high percentages of synergism, which allow the elaboration of new treatment hypotheses and point out some candidate combinations to be evaluated in experimental models in vivo. |
publishDate |
2018 |
dc.date.issued.fl_str_mv |
2018-07-19 |
dc.date.accessioned.fl_str_mv |
2019-10-25T21:21:09Z |
dc.date.available.fl_str_mv |
2019-10-25T21:21:09Z |
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.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/18687 |
url |
http://repositorio.ufsm.br/handle/1/18687 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
400300000005 |
dc.relation.confidence.fl_str_mv |
600 |
dc.relation.authority.fl_str_mv |
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dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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openAccess |
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Universidade Federal de Santa Maria Centro de Ciências da Saúde |
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Programa de Pós-Graduação em Farmacologia |
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UFSM |
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Brasil |
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Farmacologia |
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Universidade Federal de Santa Maria Centro de Ciências da Saúde |
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Universidade Federal de Santa Maria (UFSM) |
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UFSM |
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Biblioteca Digital de Teses e Dissertações do UFSM |
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Biblioteca Digital de Teses e Dissertações do UFSM |
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Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM) |
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atendimento.sib@ufsm.br||tedebc@gmail.com |
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