Efeito tripanocida de substâncias presentes no cajueiro ( Anacardium occidentale): uma abordagem experimental e teórica

Detalhes bibliográficos
Ano de defesa: 2020
Autor(a) principal: Marinho, Márcia Machado
Orientador(a): Martins, Alice Maria Costa
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: http://www.repositorio.ufc.br/handle/riufc/50512
Resumo: Endemic in 21 countries in Latin America, Chagas disease, caused by Trypanosoma cruzi, kills more people in the region each year than any other disease caused by parasites, including malaria. Northeastern Brazil is the second endemic region for Chagas disease in the country. Due to the caatinga vegetation and still very precarious human dwellings, in Ceará we find a great diversity of triatomines such as Triatoma pseudomaculata, Triatoma brasiliensis and Panstrongylus megistus, important in the transmission of the disease in the state, being a state with a high prevalence of the disease. In Brazil, only benznidazole is used for the treatment of Chagas disease, requiring an urgent search for new, more effective and safe drugs. Thus, the present work aimed to study the trypanocidal effect of substances present in the cashew tree (Anacardium occidentale) on the evolutionary forms of the Y strain of Trypanosoma cruzi, in an experimental and theoretical approach. The cashew leaf infusion and anacardic acid were evaluated on the evolutionary forms of T. cruzi, epimastigotes (24, 48 and 72 h), trypomastigotes (24 h) and amastigotes (24 h). Flow cytometry assays were also performed to evaluate the mechanisms of cell death with epimastigote forms treated with anacardic acid, with the markers 7AAD / annexin V, Rho123, H2DCFHDA and Acridine Orange. Scanning electron microscopy (MEV) was used to identify possible ultrastructural changes in epimastigote forms treated with anacardic acid. In the experimental approach, the cytotoxicity of the cashew leaf infusion evaluated in LLC-MK2 cells by the MTT method, showed that the infusion showed low cytotoxicity in the concentrations of 1800, 900 and 450 μg / mL. The concentrations that showed the greatest cytotoxic effect on epimastigotes and trypomastigotes were 225; 112.5 and 56.25 μg / mL. The infusion also had an anti-mastic effect, with a reduction (50%) in the average count of amastigotes / infected cells. As for anacardic acid, it showed a decrease of more than 50% in the number of amastigotes / 100 cells within 24 hours. As for the theoretical approach, an in silico study of anacardic acid and amentoflavone was carried out with the main pharmacological targets of T. cruzi: TcGAPDH, Cruzaína and Tripanotiona reductase. The cashew leaf infusion and anacardic acid have shown promise for the study and development of therapeutic alternatives for the treatment of Chagas disease.
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spelling Marinho, Márcia MachadoSantos, Ricardo Pires dosMartins, Alice Maria Costa2020-03-04T16:09:54Z2020-03-04T16:09:54Z2020-02-04MARINHO, M. M. Efeito tripanocida de substâncias presentes no cajueiro (Anacardium occidentale): uma abordagem experimental e teórica. 2020. 129 f. Tese (Doutorado em Ciências Farmacêuticas) - Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, 2020.http://www.repositorio.ufc.br/handle/riufc/50512Endemic in 21 countries in Latin America, Chagas disease, caused by Trypanosoma cruzi, kills more people in the region each year than any other disease caused by parasites, including malaria. Northeastern Brazil is the second endemic region for Chagas disease in the country. Due to the caatinga vegetation and still very precarious human dwellings, in Ceará we find a great diversity of triatomines such as Triatoma pseudomaculata, Triatoma brasiliensis and Panstrongylus megistus, important in the transmission of the disease in the state, being a state with a high prevalence of the disease. In Brazil, only benznidazole is used for the treatment of Chagas disease, requiring an urgent search for new, more effective and safe drugs. Thus, the present work aimed to study the trypanocidal effect of substances present in the cashew tree (Anacardium occidentale) on the evolutionary forms of the Y strain of Trypanosoma cruzi, in an experimental and theoretical approach. The cashew leaf infusion and anacardic acid were evaluated on the evolutionary forms of T. cruzi, epimastigotes (24, 48 and 72 h), trypomastigotes (24 h) and amastigotes (24 h). Flow cytometry assays were also performed to evaluate the mechanisms of cell death with epimastigote forms treated with anacardic acid, with the markers 7AAD / annexin V, Rho123, H2DCFHDA and Acridine Orange. Scanning electron microscopy (MEV) was used to identify possible ultrastructural changes in epimastigote forms treated with anacardic acid. In the experimental approach, the cytotoxicity of the cashew leaf infusion evaluated in LLC-MK2 cells by the MTT method, showed that the infusion showed low cytotoxicity in the concentrations of 1800, 900 and 450 μg / mL. The concentrations that showed the greatest cytotoxic effect on epimastigotes and trypomastigotes were 225; 112.5 and 56.25 μg / mL. The infusion also had an anti-mastic effect, with a reduction (50%) in the average count of amastigotes / infected cells. As for anacardic acid, it showed a decrease of more than 50% in the number of amastigotes / 100 cells within 24 hours. As for the theoretical approach, an in silico study of anacardic acid and amentoflavone was carried out with the main pharmacological targets of T. cruzi: TcGAPDH, Cruzaína and Tripanotiona reductase. The cashew leaf infusion and anacardic acid have shown promise for the study and development of therapeutic alternatives for the treatment of Chagas disease.Endêmica em 21 países da América Latina, a doença de Chagas, causada pelo Trypanosoma cruzi, mata mais pessoas na região a cada ano do que qualquer outra doença causada por parasitos, incluindo a malária. O nordeste brasileiro é a segunda região endêmica da doença de Chagas no país. Devido a vegetação de caatinga e habitações humanas ainda muito precárias, no Ceará encontramos uma grande diversidade de triatomíneos como Triatoma pseudomaculata, Triatoma brasiliensis e Panstrongylus megistus, importantes na transmissão da doença no estado, sendo um estado com alta prevalência da doença. No Brasil, apenas o benznidazol é utilizado para o tratamento da doença de Chagas, sendo necessária uma busca urgente de novos fármacos, mais eficazes e seguros. Dessa forma, o presente trabalho objetivou estudar o efeito tripanocida de substâncias presentes no cajueiro (Anacardium occidentale) sobre as formas evolutivas da cepa Y do Trypanosoma cruzi, em uma abordagem experimental e teórica por meio da infusão da folha de cajueiro e do ácido anacárdico 15:0 avaliados sobre as formas evolutivas do T. cruzi, epimastigotas (24, 48 e 72 h), tripomastigotas (24 h) e amastigotas (24 h). Também foram realizados ensaios de citometria de fluxo para avaliar os mecanismos de morte celular com as formas epimastigotas tratadas com o ácido anacárdico, com os marcadores 7AAD/anexina V, Rho123, H2DCFH-DA e Laranja de Acridina. Microscopia eletrônica de varredura (MEV) foi usada para identificar possíveis alterações ultraestruturais nas formas epimastigotas tratadas com o ácido anacárdico. Na abordagem experimental, a citotoxicidade da infusão da folha de cajueiro avaliada em células LLC-MK2 pelo método do MTT, mostrou que a infusão apresentou baixa citotoxicidade nas concentrações de 1800, 900 e 450 μg/mL. As concentrações que apresentaram maior efeito citotóxico em epimastigotas e tripomastigotas foram 225; 112,5 e 56,25 μg/mL. A infusão também apresentou efeito antiamastigota, com redução (50%) da contagem média de amastigotas/células infectadas. Quanto ao ácido anacárdico, demonstrou diminuição superior a 50% no número de amastigotas/100 células no tempo de 24 horas. Quanto á abordagem teórica, foi realizado um estudo in silico do ácido anacárdico e amentoflavona com os principais alvos farmacológicos do T. cruzi: TcGAPDH, Cruzaína e Tripanotiona redutase. A infusão da folha do cajueiro e o ácido anacárdico mostraram-se promissoras para o estudo e desenvolvimento de alternativas terapêuticas para o tratamento da doença de Chagas.Doença de ChagasTrypanosoma cruziAnacardiumEfeito tripanocida de substâncias presentes no cajueiro ( Anacardium occidentale): uma abordagem experimental e teóricainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccessORIGINAL2020_tese_mmmarinho.pdf2020_tese_mmmarinho.pdfapplication/pdf6459085http://repositorio.ufc.br/bitstream/riufc/50512/1/2020_tese_mmmarinho.pdf1c8a16d7eed6e921a3a2b3a1d30f11dfMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/50512/2/license.txt8a4605be74aa9ea9d79846c1fba20a33MD52riufc/505122020-03-04 13:09:54.894oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2020-03-04T16:09:54Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Efeito tripanocida de substâncias presentes no cajueiro ( Anacardium occidentale): uma abordagem experimental e teórica
title Efeito tripanocida de substâncias presentes no cajueiro ( Anacardium occidentale): uma abordagem experimental e teórica
spellingShingle Efeito tripanocida de substâncias presentes no cajueiro ( Anacardium occidentale): uma abordagem experimental e teórica
Marinho, Márcia Machado
Doença de Chagas
Trypanosoma cruzi
Anacardium
title_short Efeito tripanocida de substâncias presentes no cajueiro ( Anacardium occidentale): uma abordagem experimental e teórica
title_full Efeito tripanocida de substâncias presentes no cajueiro ( Anacardium occidentale): uma abordagem experimental e teórica
title_fullStr Efeito tripanocida de substâncias presentes no cajueiro ( Anacardium occidentale): uma abordagem experimental e teórica
title_full_unstemmed Efeito tripanocida de substâncias presentes no cajueiro ( Anacardium occidentale): uma abordagem experimental e teórica
title_sort Efeito tripanocida de substâncias presentes no cajueiro ( Anacardium occidentale): uma abordagem experimental e teórica
author Marinho, Márcia Machado
author_facet Marinho, Márcia Machado
author_role author
dc.contributor.co-advisor.none.fl_str_mv Santos, Ricardo Pires dos
dc.contributor.author.fl_str_mv Marinho, Márcia Machado
dc.contributor.advisor1.fl_str_mv Martins, Alice Maria Costa
contributor_str_mv Martins, Alice Maria Costa
dc.subject.por.fl_str_mv Doença de Chagas
Trypanosoma cruzi
Anacardium
topic Doença de Chagas
Trypanosoma cruzi
Anacardium
description Endemic in 21 countries in Latin America, Chagas disease, caused by Trypanosoma cruzi, kills more people in the region each year than any other disease caused by parasites, including malaria. Northeastern Brazil is the second endemic region for Chagas disease in the country. Due to the caatinga vegetation and still very precarious human dwellings, in Ceará we find a great diversity of triatomines such as Triatoma pseudomaculata, Triatoma brasiliensis and Panstrongylus megistus, important in the transmission of the disease in the state, being a state with a high prevalence of the disease. In Brazil, only benznidazole is used for the treatment of Chagas disease, requiring an urgent search for new, more effective and safe drugs. Thus, the present work aimed to study the trypanocidal effect of substances present in the cashew tree (Anacardium occidentale) on the evolutionary forms of the Y strain of Trypanosoma cruzi, in an experimental and theoretical approach. The cashew leaf infusion and anacardic acid were evaluated on the evolutionary forms of T. cruzi, epimastigotes (24, 48 and 72 h), trypomastigotes (24 h) and amastigotes (24 h). Flow cytometry assays were also performed to evaluate the mechanisms of cell death with epimastigote forms treated with anacardic acid, with the markers 7AAD / annexin V, Rho123, H2DCFHDA and Acridine Orange. Scanning electron microscopy (MEV) was used to identify possible ultrastructural changes in epimastigote forms treated with anacardic acid. In the experimental approach, the cytotoxicity of the cashew leaf infusion evaluated in LLC-MK2 cells by the MTT method, showed that the infusion showed low cytotoxicity in the concentrations of 1800, 900 and 450 μg / mL. The concentrations that showed the greatest cytotoxic effect on epimastigotes and trypomastigotes were 225; 112.5 and 56.25 μg / mL. The infusion also had an anti-mastic effect, with a reduction (50%) in the average count of amastigotes / infected cells. As for anacardic acid, it showed a decrease of more than 50% in the number of amastigotes / 100 cells within 24 hours. As for the theoretical approach, an in silico study of anacardic acid and amentoflavone was carried out with the main pharmacological targets of T. cruzi: TcGAPDH, Cruzaína and Tripanotiona reductase. The cashew leaf infusion and anacardic acid have shown promise for the study and development of therapeutic alternatives for the treatment of Chagas disease.
publishDate 2020
dc.date.accessioned.fl_str_mv 2020-03-04T16:09:54Z
dc.date.available.fl_str_mv 2020-03-04T16:09:54Z
dc.date.issued.fl_str_mv 2020-02-04
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
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dc.identifier.citation.fl_str_mv MARINHO, M. M. Efeito tripanocida de substâncias presentes no cajueiro (Anacardium occidentale): uma abordagem experimental e teórica. 2020. 129 f. Tese (Doutorado em Ciências Farmacêuticas) - Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, 2020.
dc.identifier.uri.fl_str_mv http://www.repositorio.ufc.br/handle/riufc/50512
identifier_str_mv MARINHO, M. M. Efeito tripanocida de substâncias presentes no cajueiro (Anacardium occidentale): uma abordagem experimental e teórica. 2020. 129 f. Tese (Doutorado em Ciências Farmacêuticas) - Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, 2020.
url http://www.repositorio.ufc.br/handle/riufc/50512
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