Estudo da toxicidade e atividade antitumoral do óleo essencial de hyptis umbrosa salzm. (lamiaceae) e da fenchona, seu componente majoritário
Ano de defesa: | 2013 |
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Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal da Paraíba
BR Farmacologia Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos UFPB |
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: | https://repositorio.ufpb.br/jspui/handle/tede/6822 |
Resumo: | Cancer is the name given to a collection of hundreds of different diseases that result from the progressive accumulation of mutations. Its treatment has been benefited from studies that are based on research of natural sources. Several compounds and plant derivatives have shown antitumor activity, including essential oils. Hyptis umbrosa Salzm. is popularly known as aleluia do serrote and alfazema-do-mato and is rarely reported in the literature. The fenchone monoterpene is the major component of the essential oil from the leaves of this species (24.8%). This study aimed to evaluate the toxicity and antitumor activity in vitro and in vivo of O.E.H. and fenchone. In hemolysis assay of mice erythrocytes it was obtained a CH50 value of 494.9 μg/mL for O.E.H. and greater than 3000 μg/mL for fenchone, suggesting moderate and low toxicity of the samples respectively for these non-tumor cells, which are commonly affected by antineoplastic therapy. The O.E.H. showed weaker antitumor effect in vitro on human tumor cell lines, while fenchone did not alter cell viability at any of the concentrations tested. After acute administration of O.E.H. depressant and excitatory effects were observed in central nervous system of animals treated with 2000 mg/kg of oil. Although it hasn t shown antitumor activity in vitro, O.E.H. (50, 100, or 150 mg / kg) and fenchone (30 or 60 mg / kg) showed significant activity in vivo of Ehrlich ascites carcinoma model (EAC) after nine days of treatment, given the parameters of volume, weight and viability of the cells. The treatment with O.E.H. induced cycle arrest in the G0/G1 phase and increased sub-G1, suggesting induction of cell death by apoptosis. In conjunction with the results of staining with Annexin V-PI, where there was a slight increase of cells stained with Annexin V as well as with Annexin V-PI, it can be inferred that possibly apoptotic cells were phagocytosed. The fenchone induced cycle arrest in S phase, and significantly increased the percentage of cells stained with Annexin V-PI, without increasing marking only with Annexin V, wich suggests that cell death by necrosis is occurring. There was also an increase in median survival of animals transplanted with Ehrlich tumor and treated with essential oil. The toxicological analyzes show that the treatment with O.E.H caused a body weight decrease and lower hematological and biochemical toxicity after nine days. The treatment with fenchone induced changes in ALT and AST parameters suggestive of fibrosis. Histopathologic analysis confirmed the evidence of hepatotoxicity especially for OEH, however, the damage was moderate and reversible. The O.E.H. induced an increase in the number of micronucleated erythrocytes, in the micronucleus essay, only the highest dose tested (300 mg / kg). Therefore, we can infer that O.E.H. and fenchone shows an antitumor activity in vivo with moderate toxicity, which is not a limiting factor for the continuation of the pre-clinical studies. The findings suggested that fenchone is not the only component responsible for the oil activity as it showed activity only at double of the dose associated with its quantity in that oil. |
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Estudo da toxicidade e atividade antitumoral do óleo essencial de hyptis umbrosa salzm. (lamiaceae) e da fenchona, seu componente majoritárioStudy of toxicity and antitumor activity of essential oil from hyptis umbrosa salzm. (lamiaceae) and fechona, its major componentHyptis umbrosaÓleo essencialAtividade antitumoralToxicidadeHyptis umbrosaEssential oilAntitumor activityToxicityCIENCIAS BIOLOGICAS::FARMACOLOGIACancer is the name given to a collection of hundreds of different diseases that result from the progressive accumulation of mutations. Its treatment has been benefited from studies that are based on research of natural sources. Several compounds and plant derivatives have shown antitumor activity, including essential oils. Hyptis umbrosa Salzm. is popularly known as aleluia do serrote and alfazema-do-mato and is rarely reported in the literature. The fenchone monoterpene is the major component of the essential oil from the leaves of this species (24.8%). This study aimed to evaluate the toxicity and antitumor activity in vitro and in vivo of O.E.H. and fenchone. In hemolysis assay of mice erythrocytes it was obtained a CH50 value of 494.9 μg/mL for O.E.H. and greater than 3000 μg/mL for fenchone, suggesting moderate and low toxicity of the samples respectively for these non-tumor cells, which are commonly affected by antineoplastic therapy. The O.E.H. showed weaker antitumor effect in vitro on human tumor cell lines, while fenchone did not alter cell viability at any of the concentrations tested. After acute administration of O.E.H. depressant and excitatory effects were observed in central nervous system of animals treated with 2000 mg/kg of oil. Although it hasn t shown antitumor activity in vitro, O.E.H. (50, 100, or 150 mg / kg) and fenchone (30 or 60 mg / kg) showed significant activity in vivo of Ehrlich ascites carcinoma model (EAC) after nine days of treatment, given the parameters of volume, weight and viability of the cells. The treatment with O.E.H. induced cycle arrest in the G0/G1 phase and increased sub-G1, suggesting induction of cell death by apoptosis. In conjunction with the results of staining with Annexin V-PI, where there was a slight increase of cells stained with Annexin V as well as with Annexin V-PI, it can be inferred that possibly apoptotic cells were phagocytosed. The fenchone induced cycle arrest in S phase, and significantly increased the percentage of cells stained with Annexin V-PI, without increasing marking only with Annexin V, wich suggests that cell death by necrosis is occurring. There was also an increase in median survival of animals transplanted with Ehrlich tumor and treated with essential oil. The toxicological analyzes show that the treatment with O.E.H caused a body weight decrease and lower hematological and biochemical toxicity after nine days. The treatment with fenchone induced changes in ALT and AST parameters suggestive of fibrosis. Histopathologic analysis confirmed the evidence of hepatotoxicity especially for OEH, however, the damage was moderate and reversible. The O.E.H. induced an increase in the number of micronucleated erythrocytes, in the micronucleus essay, only the highest dose tested (300 mg / kg). Therefore, we can infer that O.E.H. and fenchone shows an antitumor activity in vivo with moderate toxicity, which is not a limiting factor for the continuation of the pre-clinical studies. The findings suggested that fenchone is not the only component responsible for the oil activity as it showed activity only at double of the dose associated with its quantity in that oil.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESO câncer é o nome dado a um conjunto de centenas de doenças distintas que decorrem do acúmulo progressivo de mutações. Seu tratamento tem se beneficiado dos estudos que se baseiam em pesquisas de fontes naturais. Vários compostos e derivados vegetais têm mostrado atividade antitumoral, dentre eles, os óleos essenciais. Hyptis umbrosa Salzm. é conhecida popularmente por aleluia do serrote e alfazema-do-mato e é pouco relatada na literatura, sendo o componente majoritário do óleo essencial das folhas dessa espécie (O.E.H.) o monoterpeno fenchona (24,8%). Esse trabalho teve como objetivo avaliar a toxicidade e atividade antitumoral do O.E.H. e da fenchona em modelos in vitro e in vivo. No ensaio de hemólise em eritrócitos de camundongos o valor de CH50 obtido foi de 494,9 μg/mL para O.E.H. e superior a 3000 μg/mL para a fenchona, o que sugere moderada e baixa toxicidade das amostras, respectivamente, para essas células não tumorais que são comumente afetadas pela terapia antineoplásica. O.E.H. mostrou fraco efeito antitumoral in vitro em linhagens de células tumorais humanas, enquanto que a fenchona não alterou a viabilidade celular em nenhuma das concentrações testadas. Após administração aguda do O.E.H. em camundongos foram observados efeitos depressores e excitatórios do Sistema Nervoso Central nos animais tratados com 2000 mg/kg do óleo. O valor estimado da DL50 foi em torno de 500 mg/kg. Apesar de não apresentar atividade antitumoral in vitro, O.E.H. (50, 100 ou 150 mg/kg) e fenchona (60 mg/kg), após nove dias de tratamento, mostraram significante atividade in vivo em modelo de carcinoma ascítico de Ehrlich (EAC), considerando os parâmetros volume, peso e viabilidade celular. O tratamento com O.E.H. (150 mg/kg) induziu parada do ciclo na fase G0/G1 e aumento da fração sub-G1, o que sugere morte celular por apoptose. Em conjunto com os resultados da marcação com Anexina V-IP, onde houve pequeno aumento de células marcadas com Anexina V, bem como com Anexina V-IP, pode-se inferir que, possivelmente, as células em apoptose foram fagocitadas. A fenchona induziu parada do ciclo na fase S e aumentou significativamente a porcentagem de células marcadas com Anexina V-IP, sem aumentar a marcação apenas com Anexina V, o que sugere que está ocorrendo morte celular por necrose. Observou-se ainda, aumento na média de sobrevida dos animais transplantados com tumor de Ehrlich e tradados com o óleo essencial. As análises toxicológicas indicam que, após nove dias de tratamento com O.E.H. foi observado redução no peso corporal e baixa toxicidade hematológica e bioquímica. O tratamento com a fenchona induziu alteração nos parâmetros AST e ALT sugestivas de fibrose. A análise histopatológica indicou danos hepáticos após tratamento com O.E.H., entretanto, os danos foram considerados moderados e reversíveis. O.E.H. induziu aumento na quantidade de eritrócitos micronucleados, no ensaio do micronúcleo, apenas na maior dose testada (300 mg/kg). Portanto, é possível inferir que O.E.H. e fenchona apresentam atividade antitumoral in vivo com moderada toxicidade, o que não representa um fator limitante para a continuação de seus estudos pré-clínicos. Os dados permitem sugerir que a fenchona não é o único componente responsável pela atividade do óleo, uma vez que, mostrou atividade apenas no dobro na dose associada com sua quantidade no referido óleo.Universidade Federal da ParaíbaBRFarmacologiaPrograma de Pós-Graduação em Produtos Naturais e Sintéticos BioativosUFPBBranco, Marianna Vieira Sobral Castellohttp://lattes.cnpq.br/1036684849301560Rolim, Thaísa Leite2015-05-14T13:00:03Z2018-07-21T00:26:01Z2014-10-232018-07-21T00:26:01Z2013-09-11info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfROLIM, Thaísa Leite. Estudo da toxicidade e atividade antitumoral do óleo essencial de hyptis umbrosa salzm. (lamiaceae) e da fenchona, seu componente majoritário. 2013. 135 f. Tese (Doutorado em Produtos Naturais Sintéticos Bioativos) - Universidade Federal da Paraíba, João Pessoa, 2013.https://repositorio.ufpb.br/jspui/handle/tede/6822porinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFPBinstname:Universidade Federal da Paraíba (UFPB)instacron:UFPB2018-09-06T02:34:21Zoai:repositorio.ufpb.br:tede/6822Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufpb.br/PUBhttp://tede.biblioteca.ufpb.br:8080/oai/requestdiretoria@ufpb.br|| diretoria@ufpb.bropendoar:2018-09-06T02:34:21Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)false |
dc.title.none.fl_str_mv |
Estudo da toxicidade e atividade antitumoral do óleo essencial de hyptis umbrosa salzm. (lamiaceae) e da fenchona, seu componente majoritário Study of toxicity and antitumor activity of essential oil from hyptis umbrosa salzm. (lamiaceae) and fechona, its major component |
title |
Estudo da toxicidade e atividade antitumoral do óleo essencial de hyptis umbrosa salzm. (lamiaceae) e da fenchona, seu componente majoritário |
spellingShingle |
Estudo da toxicidade e atividade antitumoral do óleo essencial de hyptis umbrosa salzm. (lamiaceae) e da fenchona, seu componente majoritário Rolim, Thaísa Leite Hyptis umbrosa Óleo essencial Atividade antitumoral Toxicidade Hyptis umbrosa Essential oil Antitumor activity Toxicity CIENCIAS BIOLOGICAS::FARMACOLOGIA |
title_short |
Estudo da toxicidade e atividade antitumoral do óleo essencial de hyptis umbrosa salzm. (lamiaceae) e da fenchona, seu componente majoritário |
title_full |
Estudo da toxicidade e atividade antitumoral do óleo essencial de hyptis umbrosa salzm. (lamiaceae) e da fenchona, seu componente majoritário |
title_fullStr |
Estudo da toxicidade e atividade antitumoral do óleo essencial de hyptis umbrosa salzm. (lamiaceae) e da fenchona, seu componente majoritário |
title_full_unstemmed |
Estudo da toxicidade e atividade antitumoral do óleo essencial de hyptis umbrosa salzm. (lamiaceae) e da fenchona, seu componente majoritário |
title_sort |
Estudo da toxicidade e atividade antitumoral do óleo essencial de hyptis umbrosa salzm. (lamiaceae) e da fenchona, seu componente majoritário |
author |
Rolim, Thaísa Leite |
author_facet |
Rolim, Thaísa Leite |
author_role |
author |
dc.contributor.none.fl_str_mv |
Branco, Marianna Vieira Sobral Castello http://lattes.cnpq.br/1036684849301560 |
dc.contributor.author.fl_str_mv |
Rolim, Thaísa Leite |
dc.subject.por.fl_str_mv |
Hyptis umbrosa Óleo essencial Atividade antitumoral Toxicidade Hyptis umbrosa Essential oil Antitumor activity Toxicity CIENCIAS BIOLOGICAS::FARMACOLOGIA |
topic |
Hyptis umbrosa Óleo essencial Atividade antitumoral Toxicidade Hyptis umbrosa Essential oil Antitumor activity Toxicity CIENCIAS BIOLOGICAS::FARMACOLOGIA |
description |
Cancer is the name given to a collection of hundreds of different diseases that result from the progressive accumulation of mutations. Its treatment has been benefited from studies that are based on research of natural sources. Several compounds and plant derivatives have shown antitumor activity, including essential oils. Hyptis umbrosa Salzm. is popularly known as aleluia do serrote and alfazema-do-mato and is rarely reported in the literature. The fenchone monoterpene is the major component of the essential oil from the leaves of this species (24.8%). This study aimed to evaluate the toxicity and antitumor activity in vitro and in vivo of O.E.H. and fenchone. In hemolysis assay of mice erythrocytes it was obtained a CH50 value of 494.9 μg/mL for O.E.H. and greater than 3000 μg/mL for fenchone, suggesting moderate and low toxicity of the samples respectively for these non-tumor cells, which are commonly affected by antineoplastic therapy. The O.E.H. showed weaker antitumor effect in vitro on human tumor cell lines, while fenchone did not alter cell viability at any of the concentrations tested. After acute administration of O.E.H. depressant and excitatory effects were observed in central nervous system of animals treated with 2000 mg/kg of oil. Although it hasn t shown antitumor activity in vitro, O.E.H. (50, 100, or 150 mg / kg) and fenchone (30 or 60 mg / kg) showed significant activity in vivo of Ehrlich ascites carcinoma model (EAC) after nine days of treatment, given the parameters of volume, weight and viability of the cells. The treatment with O.E.H. induced cycle arrest in the G0/G1 phase and increased sub-G1, suggesting induction of cell death by apoptosis. In conjunction with the results of staining with Annexin V-PI, where there was a slight increase of cells stained with Annexin V as well as with Annexin V-PI, it can be inferred that possibly apoptotic cells were phagocytosed. The fenchone induced cycle arrest in S phase, and significantly increased the percentage of cells stained with Annexin V-PI, without increasing marking only with Annexin V, wich suggests that cell death by necrosis is occurring. There was also an increase in median survival of animals transplanted with Ehrlich tumor and treated with essential oil. The toxicological analyzes show that the treatment with O.E.H caused a body weight decrease and lower hematological and biochemical toxicity after nine days. The treatment with fenchone induced changes in ALT and AST parameters suggestive of fibrosis. Histopathologic analysis confirmed the evidence of hepatotoxicity especially for OEH, however, the damage was moderate and reversible. The O.E.H. induced an increase in the number of micronucleated erythrocytes, in the micronucleus essay, only the highest dose tested (300 mg / kg). Therefore, we can infer that O.E.H. and fenchone shows an antitumor activity in vivo with moderate toxicity, which is not a limiting factor for the continuation of the pre-clinical studies. The findings suggested that fenchone is not the only component responsible for the oil activity as it showed activity only at double of the dose associated with its quantity in that oil. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-09-11 2014-10-23 2015-05-14T13:00:03Z 2018-07-21T00:26:01Z 2018-07-21T00:26:01Z |
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 |
ROLIM, Thaísa Leite. Estudo da toxicidade e atividade antitumoral do óleo essencial de hyptis umbrosa salzm. (lamiaceae) e da fenchona, seu componente majoritário. 2013. 135 f. Tese (Doutorado em Produtos Naturais Sintéticos Bioativos) - Universidade Federal da Paraíba, João Pessoa, 2013. https://repositorio.ufpb.br/jspui/handle/tede/6822 |
identifier_str_mv |
ROLIM, Thaísa Leite. Estudo da toxicidade e atividade antitumoral do óleo essencial de hyptis umbrosa salzm. (lamiaceae) e da fenchona, seu componente majoritário. 2013. 135 f. Tese (Doutorado em Produtos Naturais Sintéticos Bioativos) - Universidade Federal da Paraíba, João Pessoa, 2013. |
url |
https://repositorio.ufpb.br/jspui/handle/tede/6822 |
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por |
language |
por |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal da Paraíba BR Farmacologia Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos UFPB |
publisher.none.fl_str_mv |
Universidade Federal da Paraíba BR 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 |
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UFPB |
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Biblioteca Digital de Teses e Dissertações da UFPB |
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Biblioteca Digital de Teses e Dissertações da UFPB |
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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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1801843146949132288 |