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Doctoral Thesis
DOI
10.11606/T.60.2010.tde-13072010-204337
Document
Author
Full name
Viviane Rodrigues Esperandim
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2010
Supervisor
Committee
Albuquerque, Sergio de (President)
Pinto, Mara Cristina
Prado Junior, Jose Clovis do
Rocha, Gutemberg de Melo
Souza, Clovis Wesley Oliveira de
Title in Portuguese
Perfil tripanocida de lignanas dibenzilbutirolactônicas: avaliação das propriedades terapêuticas in vivo nas fases aguda e crônica da doença de Chagas experimental
Keywords in Portuguese
cubebina
Doença de Chagas
fases aguda e crônica
hinoquinina.
Abstract in Portuguese
A doença de Chagas, transmitida pelo protozoário Trypanosoma cruzi, afeta mais de 18 milhões de pessoas na América Latina e mesmo tendo sido descrita há 100 anos por Carlos Chagas, esta ainda representa um importante problema de saúde pública, sendo encontrados casos em 18 países em desenvolvimento na América do Sul e Central. No Brasil, o benzonidazol, (ROCHAGAN), é a única droga de atividade tripanocida disponível no mercado mesmo apresentando vários efeitos colaterais e limitada eficácia na fase crônica da infecção. Em vista da necessidade de novas substâncias com atividade biológica sobre T.cruzi, o interesse pela pesquisa vem crescendo com o intuito de se obter compostos capazes de atuarem sobre o parasita, desprovidos dos graves efeitos colaterais. Estudos desenvolvidos em nosso laboratório envolvendo lignanas demonstraram uma importante atividade destes compostos sobre as formas tripomastigotas sanguíneas. Assim este estudo tem como objetivo avaliar a atividade terapêutica de derivados de lignana dibenzilbutirolactônicas em sistema in vivo, em fase aguda e crônica da infecção por T. cruzi. Como critérios de estudo avaliamos o comportamento parasitêmico dos animais na fase aguda, quantificamos a enzima -galactosidase nos tecidos do fígado, baço e coração além da análise morfométrica dos tecidos. Com relação à parasitemia, dos animais na fase aguda, as substâncias cubebina e hinoquina, apresentaram significante redução parasitêmica comparado ao controle negativo e melhor atividade no tratamento pela via oral. Na análise por caracterização de -galactosidase, as substâncias apresentaram melhores resultados comparados ao controle positivo (Benzonidazol) e também melhor eficácia da resposta para o tratamento pela via oral. Nos resultados apresentados pela cariometria os grupos de tratamento com as substâncias cubebina e hinoquinina apresentaram valores próximos ao controle não infectado, mostrando que ocorreu uma resposta celular positiva comparado ao controle infectado.
Title in English
Trypanocidal profile of dibenzylbutyrolactone lignans: evaluation of therapeutic properties in vivo, in acute and chronic experimental Chagas' disease
Keywords in English
acute and chronic
Chagas disease
cubebin
hinokinin.
Abstract in English
Chagas disease, transmitted by the protozoan Trypanosoma cruzi, affects over 18 million people in Latin America. Even though it was described 100 years ago by Carlos Chagas, it still represents a major public health problem, and there are cases in 18 developing countries located in Central and South America. In Brazil, benznidazole (Rochagan) is the only trypanocidal drug available in the market; however, it has several side effects and limited efficacy in the chronic phase of the infection. In view of the need for new substances with biological activity against T. cruzi, there is growing interest in the search for compounds capable of acting on the parasite, but are devoid of serious side effects. Studies involving lignans developed in our laboratory have shown that these compounds are significantly active against bloodstream trypomastigotes. So this study aims to evaluate the therapeutic activity of derivatives of dibenzylbutyrolactone lignans in vivo, in the acute and chronic infection by T. cruzi. The present study examined the degree of parasitemia in the infected animals during the acute phase of the disease. To this end, the enzyme -galactosidase was measured in the tissues from the liver, spleen, and heart of infected animals, in addition to the morphometric analysis of these tissues. Cubebin and hinokinin led to significant reduction in parasitemia compared to the negative control, and better treatment was accomplished by the oral route. Concerning -galactosidase analysis, cubebin and hinokinin furnished better results compared to the positive control (Benznidazole), the most effective response to treatment being also achieved by oral route. Karyometry also revealed that cubebin and hinokinin were effective, giving values close to those obtained with the uninfected control, thereby showing that there was a positive cellular response.
 
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Publishing Date
2010-09-24
 
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