Estudo in vitro da inativação fotodinâmica dos microrganismos causadores da esporotricose

Detalhes bibliográficos
Ano de defesa: 2023
Autor(a) principal: Rocha, Amanda Regina
Orientador(a): Bagnato, Vanderlei Salvador lattes
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal de São Carlos
Câmpus São Carlos
Programa de Pós-Graduação: Programa de Pós-Graduação em Biotecnologia - PPGBiotec
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Palavras-chave em Inglês:
Área do conhecimento CNPq:
Link de acesso: https://repositorio.ufscar.br/handle/20.500.14289/19011
Resumo: Sporotrichosis is a zoonosis caused by Sporothrix spp., a fungus that causes a subcutaneous mycosis which can become systemic in immunocompromised individuals. Conventional treatment is based on the prolonged use of antifungals, which can cause many side effects and, to improve on this, it is necessary to study efficient alternatives. The present study aims to show the effectiveness of Antimicrobial Photodynamic Therapy (aPDT) using curcumin as a photosensitizer in the control of S. brasiliensis and S. schenckii, and Candida albicans as a comparative parameter for results. In addition to showing the best parameters for combining aPDT with traditional antifungals against these microorganisms. The fungi were illuminated via a Biotable® (lighting device with 24 evenly distributed LEDs) at a wavelength of 450 nm and a light dose of 31.5 J/cm² with photosensitizer concentrations ranging from 0.75 to 150 μg/mL of curcumin. After determining the Minimum Inhibitory Concentration (MIC) of the itraconazole, ketoconazole and potassium iodide, antifungal therapy was combined with aPDT to verify whether subinhibitory doses of these drugs would be able to eliminate Sporothrix spp. Concentrations of 1.5 to 15 μg/mL of curcumin were used, and the dosages of the drugs reducing the dose from half of the MIC values obtained. An efficient protocol for the inactivation of all microorganisms studied was found with a single application of aPDT and with aPDT combined with conventional treatment. The best results were obtained with aPDT application prior to antifungals, causing the total elimination of the Sporothrix spp. in addition to C. albicans, even with underdoses of both the photosensitizer and antifungal drugs. To better understand the impact of the order of therapies, studies were made of the absorption spectrum of individual compounds and how the combination could influence the dynamics of photobleaching of these compounds. The present study suggests that aPDT using curcumin as a photosensitizer may be a promising alternative to combat sporotrichosis. This treatment would be especially effective in veterinary medicine to be applied in cats as an individual therapy or as a coadjuvant. In the combination of therapies, in vitro protocols result in a synergistic effect in the inactivation of microorganisms. This could improve the treatment of the disease, with a reduction in both the recuperation time and dosage of drugs used, significant benefits of this approach are overall cost reductions and lessened side effects due to preventing the prolonged use of antifungals, while achieving an effective overall treatment.
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spelling Rocha, Amanda ReginaBagnato, Vanderlei Salvadorhttp://lattes.cnpq.br/4947860249518663http://lattes.cnpq.br/6338455111772193https://orcid.org/0000-0001-9605-799Xhttps://orcid.org/0000-0003-4833-239X2023-12-12T20:38:15Z2023-12-12T20:38:15Z2023-06-02ROCHA, Amanda Regina. Estudo in vitro da inativação fotodinâmica dos microrganismos causadores da esporotricose. 2023. Dissertação (Mestrado em Biotecnologia) – Universidade Federal de São Carlos, São Carlos, 2023. Disponível em: https://repositorio.ufscar.br/handle/20.500.14289/19011.https://repositorio.ufscar.br/handle/20.500.14289/19011Sporotrichosis is a zoonosis caused by Sporothrix spp., a fungus that causes a subcutaneous mycosis which can become systemic in immunocompromised individuals. Conventional treatment is based on the prolonged use of antifungals, which can cause many side effects and, to improve on this, it is necessary to study efficient alternatives. The present study aims to show the effectiveness of Antimicrobial Photodynamic Therapy (aPDT) using curcumin as a photosensitizer in the control of S. brasiliensis and S. schenckii, and Candida albicans as a comparative parameter for results. In addition to showing the best parameters for combining aPDT with traditional antifungals against these microorganisms. The fungi were illuminated via a Biotable® (lighting device with 24 evenly distributed LEDs) at a wavelength of 450 nm and a light dose of 31.5 J/cm² with photosensitizer concentrations ranging from 0.75 to 150 μg/mL of curcumin. After determining the Minimum Inhibitory Concentration (MIC) of the itraconazole, ketoconazole and potassium iodide, antifungal therapy was combined with aPDT to verify whether subinhibitory doses of these drugs would be able to eliminate Sporothrix spp. Concentrations of 1.5 to 15 μg/mL of curcumin were used, and the dosages of the drugs reducing the dose from half of the MIC values obtained. An efficient protocol for the inactivation of all microorganisms studied was found with a single application of aPDT and with aPDT combined with conventional treatment. The best results were obtained with aPDT application prior to antifungals, causing the total elimination of the Sporothrix spp. in addition to C. albicans, even with underdoses of both the photosensitizer and antifungal drugs. To better understand the impact of the order of therapies, studies were made of the absorption spectrum of individual compounds and how the combination could influence the dynamics of photobleaching of these compounds. The present study suggests that aPDT using curcumin as a photosensitizer may be a promising alternative to combat sporotrichosis. This treatment would be especially effective in veterinary medicine to be applied in cats as an individual therapy or as a coadjuvant. In the combination of therapies, in vitro protocols result in a synergistic effect in the inactivation of microorganisms. This could improve the treatment of the disease, with a reduction in both the recuperation time and dosage of drugs used, significant benefits of this approach are overall cost reductions and lessened side effects due to preventing the prolonged use of antifungals, while achieving an effective overall treatment.A esporotricose é uma zoonose causada pelo Sporothrix spp., fungo causador de uma micose subcutânea que pode progredir e se tornar sistêmica em indivíduos imunocomprometidos. O tratamento convencional é baseado no uso prolongado da antifúngicos, o qual pode ocasionar muitos efeitos colaterais e, por essa razão, faz-se necessário o estudo de alternativas que sejam eficientes para o controle da doença. O presente estudo teve por objetivo mostrar a eficácia do uso da Terapia Fotodinâmica Antimicrobiana (TFDa) usando a curcumina como fotossensibilizador (FS) no controle dos fungos S. brasiliensis, S. schenckii, e a Candida albicans como parâmetro comparativo dos resultados. Além de mostrar os melhores parâmetros de combinação da TFDa com os antifúngicos tradicionais contra esses microrganismos. Os fungos foram iluminados em Biotable® (dispositivo de iluminação com 24 LEDs distribuídos uniformemente) em comprimento de onda de 450 nm e dose de luz de 31,5 J/cm2 e concentrações de fotossensibilizador que que variaram 0,75 a 150 μg/mL de curcumina. Após determinação da Concentração Inibitória Mínima (CIM) do itraconazol, cetoconazol e iodeto de potássio, a terapia antifúngica foi combinada com a TFDa para verificar se, mesmo doses subnibitórias dos fármacos utilizados seriam capazes de eliminar o Sporothrix spp. Foram utilizadas concentrações de 1,5 a 15 μg/mL de curcumina e as concentrações dos fármacos reduzindo a dose a partir da metade dos valores de CIM obtidos. Foi encontrado um protocolo eficiente de inativação de todos os microrganismos estudados com a TFDa como tratamento único e, em relação ao seu uso combinado com o tratamento convencional, os melhores resultados foram obtidos com a realização da TFDa antes dos antifúngicos, chegando à eliminação total da C. albicans, do S. brasiliensis e do S. schenckii mesmo com as subdoses tanto do fotossensibilizador como do antifúngico. Para entender o motivo pelo qual a ordem das terapias era tão importante, foram feitos estudos do espectro de absorção dos compostos individuais e de como a combinação poderia influenciar na dinâmica da fotodegradação desses compostos. O presente estudo sugere que a TFDa usando a curcumina como fotossensibilizador pode ser uma alternativa promissora no combate a esporotricose, principalmente na medicina veterinária aplicada em gatos, seja como terapia individual, seja como coadjuvante. Na associação das terapias, foram encontrados protocolos in vitro que resultaram em um efeito sinérgico na inativação dos microrganismos, podendo resultar em melhor resposta ao tratamento em relação a redução do tempo de cura e dosagem dos medicamentos usados, o que reflete em redução de custos, assim como redução de efeitos colaterais causados do pelo prolongado dos antifúngicos.OutraporUniversidade Federal de São CarlosCâmpus São CarlosPrograma de Pós-Graduação em Biotecnologia - PPGBiotecUFSCarAttribution-NonCommercial-NoDerivs 3.0 Brazilhttp://creativecommons.org/licenses/by-nc-nd/3.0/br/info:eu-repo/semantics/openAccessSporothrixTerapia fotodinâmica antimicrobianaEsporotricoseCurcuminaZoonoseDoenças tropicais negligenciadasCIENCIAS DA SAUDEEstudo in vitro da inativação fotodinâmica dos microrganismos causadores da esporotricoseIn vitro study of the Photodynamic Inactivation of sporotrichosis microorganismsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisreponame:Repositório Institucional da UFSCARinstname:Universidade Federal de São Carlos (UFSCAR)instacron:UFSCARORIGINALVERSÃO FINAL CORRIGIDA ARR DISSERTAÇÃO.pdfVERSÃO FINAL CORRIGIDA ARR DISSERTAÇÃO.pdfapplication/pdf2305089https://repositorio.ufscar.br/bitstreams/bd770efb-eef1-4efe-b053-c97828bb23b9/download49303392c9c9b677861813d128e8fdb9MD51trueAnonymousREADCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8810https://repositorio.ufscar.br/bitstreams/fa5f417e-11e7-49ec-b689-5c54acca5c54/downloadf337d95da1fce0a22c77480e5e9a7aecMD53falseAnonymousREADTEXTVERSÃO FINAL CORRIGIDA ARR DISSERTAÇÃO.pdf.txtVERSÃO FINAL CORRIGIDA ARR DISSERTAÇÃO.pdf.txtExtracted texttext/plain137399https://repositorio.ufscar.br/bitstreams/414cd660-0b5e-4c30-867d-6f3cf360ce39/downloadf44b6143d4ddbc8bd1dad9c7993031f0MD54falseAnonymousREADTHUMBNAILVERSÃO FINAL CORRIGIDA ARR DISSERTAÇÃO.pdf.jpgVERSÃO FINAL CORRIGIDA ARR DISSERTAÇÃO.pdf.jpgIM Thumbnailimage/jpeg2793https://repositorio.ufscar.br/bitstreams/a3739335-e1d3-446f-ba52-1a0e5ad81543/download5df3750ae8bb106a4d4b063c6bab5e58MD55falseAnonymousREAD20.500.14289/190112025-02-06 00:55:59.904http://creativecommons.org/licenses/by-nc-nd/3.0/br/Attribution-NonCommercial-NoDerivs 3.0 Brazilopen.accessoai:repositorio.ufscar.br:20.500.14289/19011https://repositorio.ufscar.brRepositório InstitucionalPUBhttps://repositorio.ufscar.br/oai/requestrepositorio.sibi@ufscar.bropendoar:43222025-02-06T03:55:59Repositório Institucional da UFSCAR - Universidade Federal de São Carlos (UFSCAR)false
dc.title.por.fl_str_mv Estudo in vitro da inativação fotodinâmica dos microrganismos causadores da esporotricose
dc.title.alternative.eng.fl_str_mv In vitro study of the Photodynamic Inactivation of sporotrichosis microorganisms
title Estudo in vitro da inativação fotodinâmica dos microrganismos causadores da esporotricose
spellingShingle Estudo in vitro da inativação fotodinâmica dos microrganismos causadores da esporotricose
Rocha, Amanda Regina
Sporothrix
Terapia fotodinâmica antimicrobiana
Esporotricose
Curcumina
Zoonose
Doenças tropicais negligenciadas
CIENCIAS DA SAUDE
title_short Estudo in vitro da inativação fotodinâmica dos microrganismos causadores da esporotricose
title_full Estudo in vitro da inativação fotodinâmica dos microrganismos causadores da esporotricose
title_fullStr Estudo in vitro da inativação fotodinâmica dos microrganismos causadores da esporotricose
title_full_unstemmed Estudo in vitro da inativação fotodinâmica dos microrganismos causadores da esporotricose
title_sort Estudo in vitro da inativação fotodinâmica dos microrganismos causadores da esporotricose
author Rocha, Amanda Regina
author_facet Rocha, Amanda Regina
author_role author
dc.contributor.authorlattes.por.fl_str_mv http://lattes.cnpq.br/6338455111772193
dc.contributor.authororcid.por.fl_str_mv https://orcid.org/0000-0001-9605-799X
dc.contributor.advisor1orcid.por.fl_str_mv https://orcid.org/0000-0003-4833-239X
dc.contributor.author.fl_str_mv Rocha, Amanda Regina
dc.contributor.advisor1.fl_str_mv Bagnato, Vanderlei Salvador
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/4947860249518663
contributor_str_mv Bagnato, Vanderlei Salvador
dc.subject.eng.fl_str_mv Sporothrix
topic Sporothrix
Terapia fotodinâmica antimicrobiana
Esporotricose
Curcumina
Zoonose
Doenças tropicais negligenciadas
CIENCIAS DA SAUDE
dc.subject.por.fl_str_mv Terapia fotodinâmica antimicrobiana
Esporotricose
Curcumina
Zoonose
Doenças tropicais negligenciadas
dc.subject.cnpq.fl_str_mv CIENCIAS DA SAUDE
description Sporotrichosis is a zoonosis caused by Sporothrix spp., a fungus that causes a subcutaneous mycosis which can become systemic in immunocompromised individuals. Conventional treatment is based on the prolonged use of antifungals, which can cause many side effects and, to improve on this, it is necessary to study efficient alternatives. The present study aims to show the effectiveness of Antimicrobial Photodynamic Therapy (aPDT) using curcumin as a photosensitizer in the control of S. brasiliensis and S. schenckii, and Candida albicans as a comparative parameter for results. In addition to showing the best parameters for combining aPDT with traditional antifungals against these microorganisms. The fungi were illuminated via a Biotable® (lighting device with 24 evenly distributed LEDs) at a wavelength of 450 nm and a light dose of 31.5 J/cm² with photosensitizer concentrations ranging from 0.75 to 150 μg/mL of curcumin. After determining the Minimum Inhibitory Concentration (MIC) of the itraconazole, ketoconazole and potassium iodide, antifungal therapy was combined with aPDT to verify whether subinhibitory doses of these drugs would be able to eliminate Sporothrix spp. Concentrations of 1.5 to 15 μg/mL of curcumin were used, and the dosages of the drugs reducing the dose from half of the MIC values obtained. An efficient protocol for the inactivation of all microorganisms studied was found with a single application of aPDT and with aPDT combined with conventional treatment. The best results were obtained with aPDT application prior to antifungals, causing the total elimination of the Sporothrix spp. in addition to C. albicans, even with underdoses of both the photosensitizer and antifungal drugs. To better understand the impact of the order of therapies, studies were made of the absorption spectrum of individual compounds and how the combination could influence the dynamics of photobleaching of these compounds. The present study suggests that aPDT using curcumin as a photosensitizer may be a promising alternative to combat sporotrichosis. This treatment would be especially effective in veterinary medicine to be applied in cats as an individual therapy or as a coadjuvant. In the combination of therapies, in vitro protocols result in a synergistic effect in the inactivation of microorganisms. This could improve the treatment of the disease, with a reduction in both the recuperation time and dosage of drugs used, significant benefits of this approach are overall cost reductions and lessened side effects due to preventing the prolonged use of antifungals, while achieving an effective overall treatment.
publishDate 2023
dc.date.accessioned.fl_str_mv 2023-12-12T20:38:15Z
dc.date.available.fl_str_mv 2023-12-12T20:38:15Z
dc.date.issued.fl_str_mv 2023-06-02
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dc.identifier.uri.fl_str_mv https://repositorio.ufscar.br/handle/20.500.14289/19011
identifier_str_mv ROCHA, Amanda Regina. Estudo in vitro da inativação fotodinâmica dos microrganismos causadores da esporotricose. 2023. Dissertação (Mestrado em Biotecnologia) – Universidade Federal de São Carlos, São Carlos, 2023. Disponível em: https://repositorio.ufscar.br/handle/20.500.14289/19011.
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