Efeitos da combinação de Levamisol e Lansoprazol sobre formas epimastigotas de Trypanosoma cruzi

Detalhes bibliográficos
Autor(a) principal: PIETRA PERONDI SATER
Data de Publicação: 2023
Tipo de documento: Trabalho de conclusão de curso
Idioma: por
Título da fonte: Repositório Institucional da UFMS
Texto Completo: https://repositorio.ufms.br/handle/123456789/7687
Resumo: Discovered more than 100 years ago by the brazilian doctor Carlos Justiniano Ribeiro das Chagas (1879-1934), Chagas disease, also known as American trypanosomiasis, whose etiological agent is the protozoan Trypanosoma cruzi, is among the main Neglected Tropical Diseases (NTDs). Currently, the drugs available on the market are Benznidazole and Nifurtimox, developed in the 1970s, effective in the acute phase, however, both have their effectiveness reduced as the time of infection increases and adverse reactions become more frequent. This scenario is a major contributor to the scientific community to seek new alternatives and possible strategies for the treatment of this disease. This work aims to evaluate the effects of the combination of Levamisole and Lansoprazole on epimastigote forms of Dm28c strain of T. cruzi. Levamisole is a drug commonly used as an anthelmintic and has potent immunomodulatory activity. Lansoprazole is a gastric proton pump inhibitor, advised for healing and symptomatic relief of reflux esophagitis. Based on data recently obtained by LabImunoBio (UFMS), the drug Lansoprazole shows biological activity against different life forms of T.cruzi Dm28c, and has therefore become a promising target for drug repositioning studies. Combination tests were then carried out using different concentrations of both drugs. From this, the cell viability of the parasites was analyzed by observation and determined using the MTS assay. With the calculation of viability and inhibitory concentrations, we aimed to determine the classification according to Chou (2006), as follows: strong synergism; synergism; moderate synergism; and almost additive, so that the best combination between the two drugs could be evaluated by determining the combination index of the best association. Finally, the results of this work highlight the 3:1 ratio where its inhibitory concentrations had a better value in comparison to the others.
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spelling 2023-12-03T21:15:38Z2023-12-03T21:15:38Z2023https://repositorio.ufms.br/handle/123456789/7687Discovered more than 100 years ago by the brazilian doctor Carlos Justiniano Ribeiro das Chagas (1879-1934), Chagas disease, also known as American trypanosomiasis, whose etiological agent is the protozoan Trypanosoma cruzi, is among the main Neglected Tropical Diseases (NTDs). Currently, the drugs available on the market are Benznidazole and Nifurtimox, developed in the 1970s, effective in the acute phase, however, both have their effectiveness reduced as the time of infection increases and adverse reactions become more frequent. This scenario is a major contributor to the scientific community to seek new alternatives and possible strategies for the treatment of this disease. This work aims to evaluate the effects of the combination of Levamisole and Lansoprazole on epimastigote forms of Dm28c strain of T. cruzi. Levamisole is a drug commonly used as an anthelmintic and has potent immunomodulatory activity. Lansoprazole is a gastric proton pump inhibitor, advised for healing and symptomatic relief of reflux esophagitis. Based on data recently obtained by LabImunoBio (UFMS), the drug Lansoprazole shows biological activity against different life forms of T.cruzi Dm28c, and has therefore become a promising target for drug repositioning studies. Combination tests were then carried out using different concentrations of both drugs. From this, the cell viability of the parasites was analyzed by observation and determined using the MTS assay. With the calculation of viability and inhibitory concentrations, we aimed to determine the classification according to Chou (2006), as follows: strong synergism; synergism; moderate synergism; and almost additive, so that the best combination between the two drugs could be evaluated by determining the combination index of the best association. Finally, the results of this work highlight the 3:1 ratio where its inhibitory concentrations had a better value in comparison to the others.Descoberta há mais de 100 anos atrás pelo médico brasileiro Dr. Carlos Justiniano Ribeiro das Chagas (1879-1934), a doença de Chagas, também conhecida como Tripanossomíase americana, cujo agente etiológico é o protozoário Trypanosoma cruzi, está entre as principais Doenças Tropicais Negligenciadas (DTNs). Atualmente, os fármacos disponíveis no mercado são Benznidazol e Nifurtimox, desenvolvidos nos anos 70, eficazes na fase aguda, entretanto, ambos têm sua eficácia diminuída conforme o tempo de infecção aumenta e frequentes reações adversas. Este cenário é um grande contribuínte para a comunidade científica buscar novas alternativas e possíveis estratégias para o tratamento da doença. Este trabalho teve como objetivo avaliar os efeitos da combinação entre os fármacos Levamisol e Lansoprazol sobre formas epimastigotas de T. cruzi da cepa Dm28c. Levamisol é um fármaco comumente usado como anti-helmíntico e potente atividade imunomoduladora. Lansoprazol é um inibidor da bomba de prótons gástrica, indicado para cicatrização e alívio sintomático da esofagite de refluxo. Com base em dados obtidos recentemente pelo LabImunoBio (UFMS), o fármaco Lansoprazol apresenta atividade biológica contra diferentes formas de vida de T.cruzi Dm28c, e portanto, se tornou um promissor alvo de estudos para o reposicionamento de fármacos. Foram então realizados ensaios de combinação utilizando diferentes concentrações de ambos fármacos, a partir disso, a viabilidade celular dos parasitos foi analisada por observação e determinada por meio do ensaio de MTS. Com o cálculo da viabilidade e concentrações inibitórias, tivemos o intuito de determinar a classificação segundo Chou (2006), em: forte sinergismo; sinergismo; sinergismo moderado; e quase aditivo, para que assim, pudesse ser avaliada a melhor combinação entre os dois fármacos determinando o índice de combinação da melhor associação. Por fim, os resultados deste trabalho trazem destaque para a proporção 3:1 onde suas concentrações inibitórias tiveram melhor valor em relação às outras.Fundação Universidade Federal de Mato Grosso do SulUFMSCiências Biológicasdoença de ChagasTrypanosoma cruziLevamisolLansoprazol.Efeitos da combinação de Levamisol e Lansoprazol sobre formas epimastigotas de Trypanosoma cruziinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/bachelorThesisALDA MARIA TEIXEIRA FERREIRAPIETRA PERONDI SATERinfo:eu-repo/semantics/openAccessporreponame:Repositório Institucional da UFMSinstname:Universidade Federal de Mato Grosso do Sul (UFMS)instacron:UFMSORIGINAL9585.pdf9585.pdfapplication/pdf710987https://repositorio.ufms.br/bitstream/123456789/7687/-1/9585.pdf5593a6c95365880e314454dd04b8774aMD5-1123456789/76872023-12-03 17:15:38.997oai:repositorio.ufms.br:123456789/7687Repositório InstitucionalPUBhttps://repositorio.ufms.br/oai/requestri.prograd@ufms.bropendoar:21242023-12-03T21:15:38Repositório Institucional da UFMS - Universidade Federal de Mato Grosso do Sul (UFMS)false
dc.title.pt_BR.fl_str_mv Efeitos da combinação de Levamisol e Lansoprazol sobre formas epimastigotas de Trypanosoma cruzi
title Efeitos da combinação de Levamisol e Lansoprazol sobre formas epimastigotas de Trypanosoma cruzi
spellingShingle Efeitos da combinação de Levamisol e Lansoprazol sobre formas epimastigotas de Trypanosoma cruzi
PIETRA PERONDI SATER
doença de Chagas
Trypanosoma cruzi
Levamisol
Lansoprazol.
Ciências Biológicas
title_short Efeitos da combinação de Levamisol e Lansoprazol sobre formas epimastigotas de Trypanosoma cruzi
title_full Efeitos da combinação de Levamisol e Lansoprazol sobre formas epimastigotas de Trypanosoma cruzi
title_fullStr Efeitos da combinação de Levamisol e Lansoprazol sobre formas epimastigotas de Trypanosoma cruzi
title_full_unstemmed Efeitos da combinação de Levamisol e Lansoprazol sobre formas epimastigotas de Trypanosoma cruzi
title_sort Efeitos da combinação de Levamisol e Lansoprazol sobre formas epimastigotas de Trypanosoma cruzi
author PIETRA PERONDI SATER
author_facet PIETRA PERONDI SATER
author_role author
dc.contributor.advisor1.fl_str_mv ALDA MARIA TEIXEIRA FERREIRA
dc.contributor.author.fl_str_mv PIETRA PERONDI SATER
contributor_str_mv ALDA MARIA TEIXEIRA FERREIRA
dc.subject.por.fl_str_mv doença de Chagas
Trypanosoma cruzi
Levamisol
Lansoprazol.
topic doença de Chagas
Trypanosoma cruzi
Levamisol
Lansoprazol.
Ciências Biológicas
dc.subject.classification.pt_BR.fl_str_mv Ciências Biológicas
description Discovered more than 100 years ago by the brazilian doctor Carlos Justiniano Ribeiro das Chagas (1879-1934), Chagas disease, also known as American trypanosomiasis, whose etiological agent is the protozoan Trypanosoma cruzi, is among the main Neglected Tropical Diseases (NTDs). Currently, the drugs available on the market are Benznidazole and Nifurtimox, developed in the 1970s, effective in the acute phase, however, both have their effectiveness reduced as the time of infection increases and adverse reactions become more frequent. This scenario is a major contributor to the scientific community to seek new alternatives and possible strategies for the treatment of this disease. This work aims to evaluate the effects of the combination of Levamisole and Lansoprazole on epimastigote forms of Dm28c strain of T. cruzi. Levamisole is a drug commonly used as an anthelmintic and has potent immunomodulatory activity. Lansoprazole is a gastric proton pump inhibitor, advised for healing and symptomatic relief of reflux esophagitis. Based on data recently obtained by LabImunoBio (UFMS), the drug Lansoprazole shows biological activity against different life forms of T.cruzi Dm28c, and has therefore become a promising target for drug repositioning studies. Combination tests were then carried out using different concentrations of both drugs. From this, the cell viability of the parasites was analyzed by observation and determined using the MTS assay. With the calculation of viability and inhibitory concentrations, we aimed to determine the classification according to Chou (2006), as follows: strong synergism; synergism; moderate synergism; and almost additive, so that the best combination between the two drugs could be evaluated by determining the combination index of the best association. Finally, the results of this work highlight the 3:1 ratio where its inhibitory concentrations had a better value in comparison to the others.
publishDate 2023
dc.date.accessioned.fl_str_mv 2023-12-03T21:15:38Z
dc.date.available.fl_str_mv 2023-12-03T21:15:38Z
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publisher.none.fl_str_mv Fundação Universidade Federal de Mato Grosso do Sul
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