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Master's Dissertation
DOI
Document
Author
Full name
Ferdinando de Paula Silva
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2017
Supervisor
Committee
Abrahão, Ana Amelia Carraro (President)
Pereira, Vanessa Carregaro
Prado Junior, Jose Clovis do
Title in Portuguese
Grelina: possíveis efeitos cardioprotetores e imunomoduladores na doença de Chagas experimental aguda
Keywords in Portuguese
Doença de Chagas
Grelina
Imunomodulação
Trypanosoma cruzi
Abstract in Portuguese
A doença de Chagas, causada por um protozoário flagelado denominado Trypanosoma cruzi, acomete milhares de pessoas ao redor do mundo. O tratamento continua parcialmente ineficaz, envolvendo terapias específicas dirigidas ao parasita assim como terapias adjuvantes em conduta para as manifestações clínicas. No Brasil, o benzonidazol (N-benzil-2-nitroimidazol-1-acetamida) vem sendo o único medicamento disponível para o tratamento etiológico da doença, porém pode causar efeitos colaterais aos pacientes infectados. Há emergente necessidade de avaliar o potencial de novas drogas para modular o sistema imune em resposta a agressão parasitária. A grelina tem demonstrado, em estudos recentes, ser uma importante substância com função cardioprotetora, vasodilatadora, anti-apoptótica e antioxidativa. No entanto, pouco se sabe da ação imunomoduladora da grelina na doença de Chagas. O objetivo deste estudo foi avaliar os efeitos cardioprotetores e imunomoduladores da grelina em ratos Wistar machos infectados pela cepa Y de T. cruzi. Foram analisados os seguintes parâmetros: quantificação dos parasitas sanguíneos e teciduais, análise de marcadores celulares (CD3+, CD4+, CD8+, NK, NKT, CD45RA+, macrophage e RT1B+) e produção de óxido nítrico. Além disso, outros parâmetros foram analisados, entre eles, os ensaios de linfoproliferação, apoptose de esplenócitos e avaliação de registros eletrocardiográficos. A grelina por si só não ocasionou uma diminuição da parasitemia sanguínea, tecidual ou na quantificação de óxido nítrico, porém exerceu com maestria sua ação anti-apoptótica e antiinflamatória conferindo redução do processo inflamatório cardíaco e da destruição tecidual. A associação com benzonidazol não proporcionou uma potencialização da resposta imune
Title in English
Ghrelin: possible cardioprotective and immunomodulatory effects in acute experimental phase of Chaga's disease
Keywords in English
Chagas disease
Ghrelin
Immunomodulation
Trypanosoma cruzi
Abstract in English
Chaga's disease, caused by the flagellate protozoan Trypanosoma cruzi, affects thousands of people around the world. The treatment remains partially ineffective, involving targeted therapies directed to the parasite as well as adjuvant therapies for the clinical manifestations. In Brazil, the benzonidazole (N-benzyl-2-nitroimidazol-1- acetamide) is the only drug available for the etiological treatment of the disease, with several side effects. There is an emerging need to evaluate potential new drugs to modulate the immune system against the parasitic aggression. Ghrelin a peptide hormone has been pointed as a substance with important cardioprotective, vasodilatory, anti-apoptotic and anti-oxidative functions. The lack of literature concerning to the immunomodulatory action of ghrelin in Chagas' disease, turns this work inedit. For that, the objectives of this study was to evaluate the cardioprotective and immunomodulatory effects of ghrelin in male Wistar rats infected with the Y strain of T. cruzi. The following parameters were analyzed: quantification of blood and tissue parasites, analysis of cell markers (CD3+, CD4+, CD8+, NK, NKT, CD45RA+, macrophage and RT1B+), nitric oxide production, lymphoproliferation assays, splenocyte apoptosis and evaluation electrocardiographic records. Ghrelin alone did not exert any action in reducing blood or tissue parasitemia, as well as the nitric oxide quantification, but it exerted with mastery its anti-apoptotic and antiinflammatory actions triggering a reduction of the cardiac inflammatory process and tissue destruction. The combination with benzonidazole did not provide a synergic action of the immune response
 
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Release Date
2019-07-05
Publishing Date
2017-07-27
 
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