Efeito do produto natural 2'',3''-diidrochnaflavona sobre Trypanosoma cruzi, cepa Y

Detalhes bibliográficos
Ano de defesa: 2016
Autor(a) principal: Florencio, Melissa Cristina Moraes lattes
Orientador(a): Silva, Lucia Helena Pinto da lattes
Banca de defesa: Lima, Patr?cia Fampa Negreiros lattes, Lima, Juliana Echevarria Neves de lattes, Chaves, Douglas Siqueira de Almeida lattes, Menna-Barreto, Rubem Figueiredo Sadok lattes
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal Rural do Rio de Janeiro
Programa de Pós-Graduação: Programa de P?s-Gradua??o em Ci?ncias Veterin?rias
Departamento: Instituto de Veterin?ria
País: Brasil
Palavras-chave em Português:
Doen?a de Chagas
Luxemburgia nobilis
Biflavonoide
Palavras-chave em Inglês:
Chagas disease
Luxemburgia nobilis
Biflavonoid
Área do conhecimento CNPq:
Medicina Veterin?ria
Link de acesso: https://tede.ufrrj.br/jspui/handle/jspui/6111
Resumo: Trypanosoma cruzi is the causative agent of Chagas disease which affects 8 million people in Latin America. Due to parasite high capacity to evade host immune system, and low efficacy combined to serious side effects to patients caused by available drugs against Chagas disease, the identification of alternative therapeutics is essential. Brazilian flora exhibits an immense diversity of metabolites that could fill these requirements. 2??,3??-dihydrochnaflavone is a biflavonoide extracted from Luxemburgia nobilis. In the present work, we investigated the action of 2??,3??-dihydrochnaflavone against T. cruzi (Y strain). Our experiments showed that this compound is effective against parasite epimastigotes forms, presenting IC50 value of 2.5 ?M after 96 h of treatment. The effect of the compound didn?t show dose-dependent effect at the tested concentrations. Morphological alterations were also detected in treated parasites such as mitochondrial swelling and lipid bodies accumulation observed by electronic microscopy. We investigated the lipid intensity in epimastigotes treated with 7.5 ?M of the biflavonoid for 4 days by Nile Red fluorescence labeling either by fluorometric quantification or fluorescence microscopy, but there was no significant difference compared to untreated parasites. We also observed that if the tested drugs affected intracellular amastigotes forms in Balb/c mice peritoneal macrophages infection assays. Treatment of infected macrophages with 2.5 and 5 ?M of the biflavonoid for 120h led to association index (percentage of infected macrophages multiplied by the mean number of amastigotes per macrophage) reduction of 72% and 85%, respectively. Nonetheless, these drugs concentrations were harmless to mice enriched population of lymphocytes as demonstrated by Trypan Blue exclusion test assay and mice peritoneal macrophages as demonstrated by Trypan Blue and XTT assays after 120h of treatment. These results indicate that 2'', 3''- dihydroochnaflavone exhibits the potential to become a new treatment proposal against Chagas' disease by presenting a low IC50 and for not being toxic to host cells. The mechanisms of action of this compound are not totally clarified, being a new field to be explored. Our data, together with other works of chemotherapy using natural products open up new possibilities for developing novel treatments with fewer side effects and less toxicity, but effective against the parasite
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spelling Silva, Lucia Helena Pinto da037.500.287-90https://orcid.org/0000-0002-7085-8649http://lattes.cnpq.br/0013386072339397Lima, Patr?cia Fampa Negreiros651.721.247-72https://orcid.org/0000-0003-3440-1622http://lattes.cnpq.br/8327606827760440Lima, Patr?cia Fampa Negreiros651.721.247-72https://orcid.org/0000-0003-3440-1622http://lattes.cnpq.br/8327606827760440Lima, Juliana Echevarria Neves dehttp://lattes.cnpq.br/7914623918450915Chaves, Douglas Siqueira de Almeidahttps://orcid.org/0000-0002-0571-9538http://lattes.cnpq.br/1864237318361425Menna-Barreto, Rubem Figueiredo Sadokhttps://orcid.org/0000-0002-1352-0641http://lattes.cnpq.br/3449332914008817125.365.537-52http://lattes.cnpq.br/3381527239868582Florencio, Melissa Cristina Moraes2022-12-07T11:31:25Z2016-02-24FLORENCIO, Melissa Cristina Moraes. Efeito do produto natural 2'',3''-diidrochnaflavona sobre Trypanosoma cruzi, cepa Y. 2016.52 f. Disserta??o (Mestrado em Ci?ncias Veterin?rias) - Instituto de Veterin?ria, Universidade Federal Rural do Rio de Janeiro, Serop?dica, 2016.https://tede.ufrrj.br/jspui/handle/jspui/6111Trypanosoma cruzi is the causative agent of Chagas disease which affects 8 million people in Latin America. Due to parasite high capacity to evade host immune system, and low efficacy combined to serious side effects to patients caused by available drugs against Chagas disease, the identification of alternative therapeutics is essential. Brazilian flora exhibits an immense diversity of metabolites that could fill these requirements. 2??,3??-dihydrochnaflavone is a biflavonoide extracted from Luxemburgia nobilis. In the present work, we investigated the action of 2??,3??-dihydrochnaflavone against T. cruzi (Y strain). Our experiments showed that this compound is effective against parasite epimastigotes forms, presenting IC50 value of 2.5 ?M after 96 h of treatment. The effect of the compound didn?t show dose-dependent effect at the tested concentrations. Morphological alterations were also detected in treated parasites such as mitochondrial swelling and lipid bodies accumulation observed by electronic microscopy. We investigated the lipid intensity in epimastigotes treated with 7.5 ?M of the biflavonoid for 4 days by Nile Red fluorescence labeling either by fluorometric quantification or fluorescence microscopy, but there was no significant difference compared to untreated parasites. We also observed that if the tested drugs affected intracellular amastigotes forms in Balb/c mice peritoneal macrophages infection assays. Treatment of infected macrophages with 2.5 and 5 ?M of the biflavonoid for 120h led to association index (percentage of infected macrophages multiplied by the mean number of amastigotes per macrophage) reduction of 72% and 85%, respectively. Nonetheless, these drugs concentrations were harmless to mice enriched population of lymphocytes as demonstrated by Trypan Blue exclusion test assay and mice peritoneal macrophages as demonstrated by Trypan Blue and XTT assays after 120h of treatment. These results indicate that 2'', 3''- dihydroochnaflavone exhibits the potential to become a new treatment proposal against Chagas' disease by presenting a low IC50 and for not being toxic to host cells. The mechanisms of action of this compound are not totally clarified, being a new field to be explored. Our data, together with other works of chemotherapy using natural products open up new possibilities for developing novel treatments with fewer side effects and less toxicity, but effective against the parasiteA doen?a de Chagas ? causada pelo protozo?rio parasito Trypanosoma cruzi, uma doen?a negligenciada que afeta aproximadamente 8 milh?es na Am?rica Latina. Dada a capacidade de o parasita de evadir o sistema imune do hospedeiro, a baixa efici?ncia dos tratamentos oferecidos e os sintomas e les?es debilitantes causados pela doen?a, ? muito importante a busca por novas terap?uticas mais eficientes. A flora brasileira possui uma imensa diversidade de metab?litos secund?rios que podem apresentar a??o antiparasit?ria. 2??,3??-di- idroochnaflavona ? um biflavonoide extra?do de Luxemburgia nobilis. No trabalho atual, investigamos o efeito de 2??,3??-Di-idroochnaflavona contra T. cruzi, cepa Y. Os resultados mostram que o composto tem a??o contra o parasita apresentando IC50 de 2,5 ?M para formas epimastigotas ap?s 96 horas de tratamento. O composto n?o demonstrou efeito dose- dependente nas concentra??es testadas. Formas epimastigotas tratadas com 2??,3??-Di- idroochnaflavona apresentaram altera??es morfol?gicas como incha?o mitocondrial e ac?mulo de corpos lip?dicos, observadas por microscopia eletr?nica. N?o foram identificadas, no entanto, altera??es na quantidade de lip?dios nos parasitos tratados e marcados com Nile Red por quantifica??o de fluoresc?ncia e microscopia de fluoresc?ncia. Experimentos preliminares mostraram que a metaciclog?nese in vitro ? alterada na presen?a do composto. Em macr?fagos peritoneais murinos de Balb/c, as formas amastigotas intracelulares foram afetadas pelo tratamento com a droga nas concentra??es de 2,5 e 5 ?M, com diminui??o de 72 e 85%, respectivamente, no ?ndice de associa??o entre os parasitas e as c?lulas hospedeiras. Nos ensaios citot?xicos, o composto n?o apresentou toxicidade para popula??o enriquecida de linf?citos de camundongos pelo m?todo de exclus?o por azul de Trypan e para macr?fagos peritoneais de camundongo pelo m?todo de exclus?o por azul de Trypan e XTT. Nossos resultados indicam que a 2??,3??-di-idroochnaflavona tem potencialidade para se tornar uma nova proposta de tratamento contra a doen?a de Chagas por apresentar um baixo IC50 e n?o ser t?xica. Os mecanismos de a??o desse composto ainda n?o foram totalmente esclarecidos, apresentando um amplo campo a ser aprofundado. Nossos dados, juntos com outros trabalhos de quimioterapia com produtos de origem natural abrem uma nova possibilidade de desenvolvimento de um tratamento com menos efeitos colaterais e menos t?xico, por?m eficiente contra o parasitoSubmitted by Celso Magalhaes (celsomagalhaes@ufrrj.br) on 2022-12-07T11:31:25Z No. of bitstreams: 1 2016 - Melissa Cristina Moraes Florencio.pdf: 1503666 bytes, checksum: 8369706825d3ad4c11123aef0864336f (MD5)Made available in DSpace on 2022-12-07T11:31:25Z (GMT). No. of bitstreams: 1 2016 - Melissa Cristina Moraes Florencio.pdf: 1503666 bytes, checksum: 8369706825d3ad4c11123aef0864336f (MD5) Previous issue date: 2016-02-24CNPq - Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gicoCAPES - Coordena??o de Aperfei?oamento de Pessoal de N?vel Superiorapplication/pdfhttps://tede.ufrrj.br/retrieve/71296/2016%20-%20Melissa%20Cristina%20Moraes%20Florencio.pdf.jpgporUniversidade Federal Rural do Rio de JaneiroPrograma de P?s-Gradua??o em Ci?ncias Veterin?riasUFRRJBrasilInstituto de Veterin?riaABDEL-SATTAR, E., MAES, L., SALAMA, M. M. In Vitro activities of plant extracts from Saudi Arabia against malaria, leishmaniasis, sleeping sickness and Chagas disease. Phytotherapic Reasearch, v. 24, p. 1322?1328, 2010. ADADE, C.M., CONS, B.L., MELO, P.A., SOUTO-PADR?N, T. Effect of Crotalus viridis viridis snake venom on the ultrastructure and intracelular survival of Trypanosoma cruzi. Parasitology, 138,46?58, 2010. 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dc.title.por.fl_str_mv Efeito do produto natural 2'',3''-diidrochnaflavona sobre Trypanosoma cruzi, cepa Y
dc.title.alternative.eng.fl_str_mv Effect of the natural product 2',3'-dihydrochnaflavone on Trypanosoma cruzi, strain Y
title Efeito do produto natural 2'',3''-diidrochnaflavona sobre Trypanosoma cruzi, cepa Y
spellingShingle Efeito do produto natural 2'',3''-diidrochnaflavona sobre Trypanosoma cruzi, cepa Y
Florencio, Melissa Cristina Moraes
Doen?a de Chagas
Luxemburgia nobilis
Biflavonoide
Chagas disease
Luxemburgia nobilis
Biflavonoid
Medicina Veterin?ria
title_short Efeito do produto natural 2'',3''-diidrochnaflavona sobre Trypanosoma cruzi, cepa Y
title_full Efeito do produto natural 2'',3''-diidrochnaflavona sobre Trypanosoma cruzi, cepa Y
title_fullStr Efeito do produto natural 2'',3''-diidrochnaflavona sobre Trypanosoma cruzi, cepa Y
title_full_unstemmed Efeito do produto natural 2'',3''-diidrochnaflavona sobre Trypanosoma cruzi, cepa Y
title_sort Efeito do produto natural 2'',3''-diidrochnaflavona sobre Trypanosoma cruzi, cepa Y
author Florencio, Melissa Cristina Moraes
author_facet Florencio, Melissa Cristina Moraes
author_role author
dc.contributor.advisor1.fl_str_mv Silva, Lucia Helena Pinto da
dc.contributor.advisor1ID.fl_str_mv 037.500.287-90
https://orcid.org/0000-0002-7085-8649
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/0013386072339397
dc.contributor.advisor-co1.fl_str_mv Lima, Patr?cia Fampa Negreiros
dc.contributor.advisor-co1ID.fl_str_mv 651.721.247-72
https://orcid.org/0000-0003-3440-1622
dc.contributor.advisor-co1Lattes.fl_str_mv http://lattes.cnpq.br/8327606827760440
dc.contributor.referee1.fl_str_mv Lima, Patr?cia Fampa Negreiros
dc.contributor.referee1ID.fl_str_mv 651.721.247-72
https://orcid.org/0000-0003-3440-1622
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/8327606827760440
dc.contributor.referee2.fl_str_mv Lima, Juliana Echevarria Neves de
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/7914623918450915
dc.contributor.referee3.fl_str_mv Chaves, Douglas Siqueira de Almeida
dc.contributor.referee3ID.fl_str_mv https://orcid.org/0000-0002-0571-9538
dc.contributor.referee3Lattes.fl_str_mv http://lattes.cnpq.br/1864237318361425
dc.contributor.referee4.fl_str_mv Menna-Barreto, Rubem Figueiredo Sadok
dc.contributor.referee4ID.fl_str_mv https://orcid.org/0000-0002-1352-0641
dc.contributor.referee4Lattes.fl_str_mv http://lattes.cnpq.br/3449332914008817
dc.contributor.authorID.fl_str_mv 125.365.537-52
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/3381527239868582
dc.contributor.author.fl_str_mv Florencio, Melissa Cristina Moraes
contributor_str_mv Silva, Lucia Helena Pinto da
Lima, Patr?cia Fampa Negreiros
Lima, Patr?cia Fampa Negreiros
Lima, Juliana Echevarria Neves de
Chaves, Douglas Siqueira de Almeida
Menna-Barreto, Rubem Figueiredo Sadok
dc.subject.por.fl_str_mv Doen?a de Chagas
Luxemburgia nobilis
Biflavonoide
topic Doen?a de Chagas
Luxemburgia nobilis
Biflavonoide
Chagas disease
Luxemburgia nobilis
Biflavonoid
Medicina Veterin?ria
dc.subject.eng.fl_str_mv Chagas disease
Luxemburgia nobilis
Biflavonoid
dc.subject.cnpq.fl_str_mv Medicina Veterin?ria
description Trypanosoma cruzi is the causative agent of Chagas disease which affects 8 million people in Latin America. Due to parasite high capacity to evade host immune system, and low efficacy combined to serious side effects to patients caused by available drugs against Chagas disease, the identification of alternative therapeutics is essential. Brazilian flora exhibits an immense diversity of metabolites that could fill these requirements. 2??,3??-dihydrochnaflavone is a biflavonoide extracted from Luxemburgia nobilis. In the present work, we investigated the action of 2??,3??-dihydrochnaflavone against T. cruzi (Y strain). Our experiments showed that this compound is effective against parasite epimastigotes forms, presenting IC50 value of 2.5 ?M after 96 h of treatment. The effect of the compound didn?t show dose-dependent effect at the tested concentrations. Morphological alterations were also detected in treated parasites such as mitochondrial swelling and lipid bodies accumulation observed by electronic microscopy. We investigated the lipid intensity in epimastigotes treated with 7.5 ?M of the biflavonoid for 4 days by Nile Red fluorescence labeling either by fluorometric quantification or fluorescence microscopy, but there was no significant difference compared to untreated parasites. We also observed that if the tested drugs affected intracellular amastigotes forms in Balb/c mice peritoneal macrophages infection assays. Treatment of infected macrophages with 2.5 and 5 ?M of the biflavonoid for 120h led to association index (percentage of infected macrophages multiplied by the mean number of amastigotes per macrophage) reduction of 72% and 85%, respectively. Nonetheless, these drugs concentrations were harmless to mice enriched population of lymphocytes as demonstrated by Trypan Blue exclusion test assay and mice peritoneal macrophages as demonstrated by Trypan Blue and XTT assays after 120h of treatment. These results indicate that 2'', 3''- dihydroochnaflavone exhibits the potential to become a new treatment proposal against Chagas' disease by presenting a low IC50 and for not being toxic to host cells. The mechanisms of action of this compound are not totally clarified, being a new field to be explored. Our data, together with other works of chemotherapy using natural products open up new possibilities for developing novel treatments with fewer side effects and less toxicity, but effective against the parasite
publishDate 2016
dc.date.issued.fl_str_mv 2016-02-24
dc.date.accessioned.fl_str_mv 2022-12-07T11:31:25Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.citation.fl_str_mv FLORENCIO, Melissa Cristina Moraes. Efeito do produto natural 2'',3''-diidrochnaflavona sobre Trypanosoma cruzi, cepa Y. 2016.52 f. Disserta??o (Mestrado em Ci?ncias Veterin?rias) - Instituto de Veterin?ria, Universidade Federal Rural do Rio de Janeiro, Serop?dica, 2016.
dc.identifier.uri.fl_str_mv https://tede.ufrrj.br/jspui/handle/jspui/6111
identifier_str_mv FLORENCIO, Melissa Cristina Moraes. Efeito do produto natural 2'',3''-diidrochnaflavona sobre Trypanosoma cruzi, cepa Y. 2016.52 f. Disserta??o (Mestrado em Ci?ncias Veterin?rias) - Instituto de Veterin?ria, Universidade Federal Rural do Rio de Janeiro, Serop?dica, 2016.
url https://tede.ufrrj.br/jspui/handle/jspui/6111
dc.language.iso.fl_str_mv por
language por
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