Avaliação da toxicidade e atividade antifúngica In Vitro do Timol sobre linhagens de Penicillium Citrinum
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UFPB |
Texto Completo: | https://repositorio.ufpb.br/jspui/handle/123456789/12807 |
Resumo: | Fungi of the genus Penicillium can be found in various substrates and affect immunocompromised people, hospitalized patients, many animals and plants, as well as compromise the quality of air indoors. The indiscriminate use of antibiotics and the resulting framework of resistance of microorganisms to conventional antimicrobial therapy has been stimulating researchers to seek alternative sources of antimicrobial compounds, among them the medicinal plants and their phytochemicals. It is also known that natural products are not free from the possibility of toxic or adverse effects and, therefore, study their toxicity is fundamental. In this context, the present study evaluated the in vitro antifungal activity of seven phytochemicals (geraniol, thymol, carvacrol, citral, r-citronellal, s-citronellal, 7-hydroxy-citronellal, citronellal and isoeugenol) on 12 strains of Penicillium citrinum, by microdilution test, selecting the one that presented the best activity for the continuation of the tests. For the accomplishment of antioxidant activity and cytotoxicity studies human red blood cells obtained from the blood bank of the Lauro Wanderley University Hospital were used. The embryotoxicity study used embryonic cells of sea urchin (Echinometra lucunter). It was verified that thymol presented the best biological activity among the phytochemicals tested, inhibiting the growth of 100% of the strains at the concentration of 64 μg / mL (MIC) and showing fungicidal activity for 50% of the strains. The peracetic acid presented antifungal activity only in the concentration corresponding to the high level of disinfection proposed by the manufacturer, with MIC of 10,000 μg / mL. The antifungal standard presented MIC50 of 8 μg / mL and MIC90 corresponding to 256 μg / mL. Thymol presented CFM values similar to the MIC values for 1/4 of the strains, while voriconazole showed it for 1/6 of the strains. The antifungal effect of thymol and the control sanitizer was not due to the destabilization of the cell wall or to the complexation with the ergosterol of the plasma membrane. No additivity, synergism or antagonism were found resulting from the combination of timol-voriconazole, evaluated by the checkerboard method. Thymol showed good oral bioavailability and showed no mutagenic, tumorigenic or reproductive effects through in silico analysis. These data were confirmed by in vitro toxicity analyzes, which revealed: low erythrocyte cytotoxicity, with hemolysis values only for blood type O and below 5%; decreased erythrocyte damage caused by osmotic stress; significant antioxidant activity for B and O blood types; besides the absence of antimitotic activity in embryonic cells of sea urchin. These results suggest that thymol represents a new and promising possibility among products with antifungal activity against Penicillium citrinum, in addition to presenting significant antioxidant activity and some degree of protection of erythrocytes against osmotic stress. |
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Avaliação da toxicidade e atividade antifúngica In Vitro do Timol sobre linhagens de Penicillium CitrinumTimolPenicillium citrinumAtividade antifúngicaCitotoxicidadeDesenvolvimento embrionárioThymolAntifungal activityCytotoxicityEmbrionary developmentCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAFungi of the genus Penicillium can be found in various substrates and affect immunocompromised people, hospitalized patients, many animals and plants, as well as compromise the quality of air indoors. The indiscriminate use of antibiotics and the resulting framework of resistance of microorganisms to conventional antimicrobial therapy has been stimulating researchers to seek alternative sources of antimicrobial compounds, among them the medicinal plants and their phytochemicals. It is also known that natural products are not free from the possibility of toxic or adverse effects and, therefore, study their toxicity is fundamental. In this context, the present study evaluated the in vitro antifungal activity of seven phytochemicals (geraniol, thymol, carvacrol, citral, r-citronellal, s-citronellal, 7-hydroxy-citronellal, citronellal and isoeugenol) on 12 strains of Penicillium citrinum, by microdilution test, selecting the one that presented the best activity for the continuation of the tests. For the accomplishment of antioxidant activity and cytotoxicity studies human red blood cells obtained from the blood bank of the Lauro Wanderley University Hospital were used. The embryotoxicity study used embryonic cells of sea urchin (Echinometra lucunter). It was verified that thymol presented the best biological activity among the phytochemicals tested, inhibiting the growth of 100% of the strains at the concentration of 64 μg / mL (MIC) and showing fungicidal activity for 50% of the strains. The peracetic acid presented antifungal activity only in the concentration corresponding to the high level of disinfection proposed by the manufacturer, with MIC of 10,000 μg / mL. The antifungal standard presented MIC50 of 8 μg / mL and MIC90 corresponding to 256 μg / mL. Thymol presented CFM values similar to the MIC values for 1/4 of the strains, while voriconazole showed it for 1/6 of the strains. The antifungal effect of thymol and the control sanitizer was not due to the destabilization of the cell wall or to the complexation with the ergosterol of the plasma membrane. No additivity, synergism or antagonism were found resulting from the combination of timol-voriconazole, evaluated by the checkerboard method. Thymol showed good oral bioavailability and showed no mutagenic, tumorigenic or reproductive effects through in silico analysis. These data were confirmed by in vitro toxicity analyzes, which revealed: low erythrocyte cytotoxicity, with hemolysis values only for blood type O and below 5%; decreased erythrocyte damage caused by osmotic stress; significant antioxidant activity for B and O blood types; besides the absence of antimitotic activity in embryonic cells of sea urchin. These results suggest that thymol represents a new and promising possibility among products with antifungal activity against Penicillium citrinum, in addition to presenting significant antioxidant activity and some degree of protection of erythrocytes against osmotic stress.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESFungos do gênero Penicillium podem ser encontrados nos mais variados substratos e afetam indivíduos imunocomprometidos, pacientes hospitalizados, animais e plantas diversas, além de comprometerem a qualidade do ar de ambientes internos. O uso indiscriminado de antibióticos e o decorrente quadro de resistência dos microorganismos à terapêutica antimicrobiana convencional vêm impulsionando os pesquisadores a buscar fontes alternativas de compostos antimicrobianos, dentre elas as plantas medicinais e seus fitoconstituintes. É conhecido, também, que os produtos naturais não são livres da possibilidade de efeitos tóxicos ou adversos e, portanto, é de fundamental importância estudar sua toxicidade. Nesse contexto, o presente estudo avaliou a atividade antifúngica in vitro de sete fitoconstituintes (geraniol, timol, carvacrol, citral, r-citronelal, s-citronelal, 7-hidróxi-citronelal, citronelal e isoeugenol) sobre doze linhagens de Penicillium citrinum, por meio do teste de microdiluição, selecionando-se o que apresentou melhor atividade para o prosseguimento dos testes. Para a realização dos estudos de atividade antioxidante e citotoxicidade foram utilizadas hemácias humanas obtidas do banco de sangue do Hospital Universitário Lauro Wanderley. O estudo da embriotoxicidade utilizou células embrionárias de ouriço-do-mar (Echinometra lucunter). Verificou-se que o timol apresentou a melhor atividade biológica dentre os fitoconstituintes testados, inibindo o crescimento de 100% das linhagens na concentração de 64 µg/mL (CIM) e apresentando atividade do tipo fungicida para 50% das linhagens. O ácido peracético apresentou atividade antifúngica apenas na concentração correspondente ao alto nível de desinfecção proposto pelo fabricante, com CIM de 10.000 μg/mL. O antifúngico padrão apresentou CIM50 de 8 μg/mL e CIM90 correspondente a 256 μg/mL. O timol apresentou valores de CFM semelhante aos valores da CIM para 1/4 das linhagens, enquanto o voriconazol, para 1/6 das linhagens. O efeito antifúngico do timol e do sanitizante controle não se deu pela desestabilização da parede celular ou pela complexação com o ergosterol da membrana plasmática. Não foram encontrados aditividade, sinergismo ou antagonismo resultantes da associação timol-voriconazol, avaliada pelo método de checkerboard. O timol demonstrou, por meio da análise in silico, boa biodisponibilidade oral e não apresentou efeitos mutagênico, tumorigênico ou reprodutivo. Estes dados foram confirmados pelas análises de toxicidade in vitro, as quais revelaram: baixa citotoxicidade frente a eritrócitos, com valores de hemólise apenas para o tipo sanguíneo O e abaixo dos 5%; diminuição dos danos eritrocitários causados pelo estresse osmótico; atividade antioxidante significativa para os tipos sanguíneos B e O; além de ausência de atividade antimitótica em células embrionárias de ouriço-do-mar. Estes resultados sugerem que o timol representa uma nova e promissora possibilidade entre os produtos com atividade antifúngica contra Penicillium citrinum, além de apresentar atividade antioxidante significativa e algum grau de proteção de eritrócitos frente ao estresse osmótico.Universidade Federal da ParaíbaBrasilFarmacologiaPrograma de Pós-Graduação em Produtos Naturais e Sintéticos BioativosUFPBLima, Edeltrudes de Oliveirahttp://lattes.cnpq.br/9406572870167006Dantas, Tassiana Barbosa2019-01-07T18:51:04Z2019-01-072019-01-07T18:51:04Z2017-10-18info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesishttps://repositorio.ufpb.br/jspui/handle/123456789/12807porAttribution-NoDerivs 3.0 Brazilhttp://creativecommons.org/licenses/by-nd/3.0/br/info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFPBinstname:Universidade Federal da Paraíba (UFPB)instacron:UFPB2019-01-07T18:51:04Zoai:repositorio.ufpb.br:123456789/12807Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufpb.br/PUBhttp://tede.biblioteca.ufpb.br:8080/oai/requestdiretoria@ufpb.br|| diretoria@ufpb.bropendoar:2019-01-07T18:51:04Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)false |
dc.title.none.fl_str_mv |
Avaliação da toxicidade e atividade antifúngica In Vitro do Timol sobre linhagens de Penicillium Citrinum |
title |
Avaliação da toxicidade e atividade antifúngica In Vitro do Timol sobre linhagens de Penicillium Citrinum |
spellingShingle |
Avaliação da toxicidade e atividade antifúngica In Vitro do Timol sobre linhagens de Penicillium Citrinum Dantas, Tassiana Barbosa Timol Penicillium citrinum Atividade antifúngica Citotoxicidade Desenvolvimento embrionário Thymol Antifungal activity Cytotoxicity Embrionary development CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
title_short |
Avaliação da toxicidade e atividade antifúngica In Vitro do Timol sobre linhagens de Penicillium Citrinum |
title_full |
Avaliação da toxicidade e atividade antifúngica In Vitro do Timol sobre linhagens de Penicillium Citrinum |
title_fullStr |
Avaliação da toxicidade e atividade antifúngica In Vitro do Timol sobre linhagens de Penicillium Citrinum |
title_full_unstemmed |
Avaliação da toxicidade e atividade antifúngica In Vitro do Timol sobre linhagens de Penicillium Citrinum |
title_sort |
Avaliação da toxicidade e atividade antifúngica In Vitro do Timol sobre linhagens de Penicillium Citrinum |
author |
Dantas, Tassiana Barbosa |
author_facet |
Dantas, Tassiana Barbosa |
author_role |
author |
dc.contributor.none.fl_str_mv |
Lima, Edeltrudes de Oliveira http://lattes.cnpq.br/9406572870167006 |
dc.contributor.author.fl_str_mv |
Dantas, Tassiana Barbosa |
dc.subject.por.fl_str_mv |
Timol Penicillium citrinum Atividade antifúngica Citotoxicidade Desenvolvimento embrionário Thymol Antifungal activity Cytotoxicity Embrionary development CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
topic |
Timol Penicillium citrinum Atividade antifúngica Citotoxicidade Desenvolvimento embrionário Thymol Antifungal activity Cytotoxicity Embrionary development CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
description |
Fungi of the genus Penicillium can be found in various substrates and affect immunocompromised people, hospitalized patients, many animals and plants, as well as compromise the quality of air indoors. The indiscriminate use of antibiotics and the resulting framework of resistance of microorganisms to conventional antimicrobial therapy has been stimulating researchers to seek alternative sources of antimicrobial compounds, among them the medicinal plants and their phytochemicals. It is also known that natural products are not free from the possibility of toxic or adverse effects and, therefore, study their toxicity is fundamental. In this context, the present study evaluated the in vitro antifungal activity of seven phytochemicals (geraniol, thymol, carvacrol, citral, r-citronellal, s-citronellal, 7-hydroxy-citronellal, citronellal and isoeugenol) on 12 strains of Penicillium citrinum, by microdilution test, selecting the one that presented the best activity for the continuation of the tests. For the accomplishment of antioxidant activity and cytotoxicity studies human red blood cells obtained from the blood bank of the Lauro Wanderley University Hospital were used. The embryotoxicity study used embryonic cells of sea urchin (Echinometra lucunter). It was verified that thymol presented the best biological activity among the phytochemicals tested, inhibiting the growth of 100% of the strains at the concentration of 64 μg / mL (MIC) and showing fungicidal activity for 50% of the strains. The peracetic acid presented antifungal activity only in the concentration corresponding to the high level of disinfection proposed by the manufacturer, with MIC of 10,000 μg / mL. The antifungal standard presented MIC50 of 8 μg / mL and MIC90 corresponding to 256 μg / mL. Thymol presented CFM values similar to the MIC values for 1/4 of the strains, while voriconazole showed it for 1/6 of the strains. The antifungal effect of thymol and the control sanitizer was not due to the destabilization of the cell wall or to the complexation with the ergosterol of the plasma membrane. No additivity, synergism or antagonism were found resulting from the combination of timol-voriconazole, evaluated by the checkerboard method. Thymol showed good oral bioavailability and showed no mutagenic, tumorigenic or reproductive effects through in silico analysis. These data were confirmed by in vitro toxicity analyzes, which revealed: low erythrocyte cytotoxicity, with hemolysis values only for blood type O and below 5%; decreased erythrocyte damage caused by osmotic stress; significant antioxidant activity for B and O blood types; besides the absence of antimitotic activity in embryonic cells of sea urchin. These results suggest that thymol represents a new and promising possibility among products with antifungal activity against Penicillium citrinum, in addition to presenting significant antioxidant activity and some degree of protection of erythrocytes against osmotic stress. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-10-18 2019-01-07T18:51:04Z 2019-01-07 2019-01-07T18:51:04Z |
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 |
https://repositorio.ufpb.br/jspui/handle/123456789/12807 |
url |
https://repositorio.ufpb.br/jspui/handle/123456789/12807 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
Attribution-NoDerivs 3.0 Brazil http://creativecommons.org/licenses/by-nd/3.0/br/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NoDerivs 3.0 Brazil http://creativecommons.org/licenses/by-nd/3.0/br/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal da Paraíba Brasil Farmacologia Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos UFPB |
publisher.none.fl_str_mv |
Universidade Federal da Paraíba Brasil Farmacologia Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos UFPB |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações da UFPB instname:Universidade Federal da Paraíba (UFPB) instacron:UFPB |
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Universidade Federal da Paraíba (UFPB) |
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UFPB |
institution |
UFPB |
reponame_str |
Biblioteca Digital de Teses e Dissertações da UFPB |
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Biblioteca Digital de Teses e Dissertações da UFPB |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB) |
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diretoria@ufpb.br|| diretoria@ufpb.br |
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