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Master's Dissertation
DOI
10.11606/D.60.2009.tde-10092009-085526
Document
Author
Full name
Christian Collins Kuehn
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2009
Supervisor
Committee
Prado Junior, Jose Clovis do (President)
Ferreira, Marcelo Urbano
Rocha, Maria Jose Alves da
Title in Portuguese
Análise in vitro e in vivo da ação conjunta dos hormônios Dehidroepiandrosterona (DHEA) e Melatonina (MEL) contra Trypanosoma cruzi
Keywords in Portuguese
Trypanosoma cruzi.
Dehidroepiandrosterona
Melatonina
Abstract in Portuguese
Estudos prévios mostram que tanto a melatonina (MEL) como a Dehidroepiandrosterona (DHEA) aumentaram a resposta imune contra distintos parasitas. O presente estudo investigou a atividade in vitro da MEL e DHEA associados em um período de 24 horas e in vivo durante o curso da infecção por T. cruzi. A atividade in vitro da MEL e DHEA sozinhos, bem como juntos foram testados sobre formas tripomastigotas (doses variando de 0.5, 8, 20, 32, 40 to 128 µM). In vitro, tanto MEL como DHEA sozinhos não mostraram qualquer atividade contras formas tripomastigotas, embora quando utilizadas em concentrações mais elevadas, a associação de MEL e DHEA mostrou-se ativa contra formas tripomastigotas do parasita. Entretanto, para estas altas concentrações, verificou-se alta toxicidade sobre os macrófagos peritoneais. Para avaliação in vivo, ratos machos Wistar foram infectados com a cepa Y de T. cruzi. Os animais foram oralmente tratados com 5 mg/kg peso corpóreo/dia de MEL e de forma subcutânea com 40mg/kg peso corpóreo/dia de DHEA. Tratamento com MEL, DHEA e associado mostrou uma redução significante no número de tripomastigotas sangüíneos durante a fase aguda da infecção quando comparado aos animais não trados (P<0.05). Um significante aumento no número de macrófagos e concentração de óxido nítrico (NO) foram observados durante o pico da parasitemia apenas com MEL ou combinado com DHEA. Entretanto, observou-se que o DHEA sozinho aumentou a concentração de NO (P<0.05), bem como os níveis de TNF-alfa durante a infecção (P<0.05). Estes resultados mostram que a MEL, DHEA ou a associação de ambos reduz a parasitemia durante a fase aguda de infecção. A ação combinada de ambos os hormônios não exerceu uma ação sinérgica sobre a magnitude da resposta imune do hospedeiro, ficando o DHEA como a substância que induziu a resposta imune mais eficiente.
Title in English
Evaluation in vitro and in vivo of the combined action of the hormones Dehydroepiandrosterone (DHEA) and Melatonin (MEL) against Trypanosoma cruzi.
Keywords in English
Trypanosoma cruzi
Dehydroepiandrosterone
Melatonin
Abstract in English
Previous studies show that melatonin (MEL) and dehydroepiandrosterone (DHEA) enhances the immune response against parasitic pathogens. The present study investigated the in vitro activity of MEL and DHEA association in a period of 24 hours and in vivo during the course of T. cruzi infection. The in vitro activity of MEL and DHEA alone, as well as together, were tested for the trypomastigote forms (doses ranging from 0.5, 8, 20, 32, 40 to 128µM). In vitro, nor MEL nor DHEA alone did not show any activity against trypomastigote forms, although when the highest concentration of MEL and DHEA association was used, it was active against the trypomastigote forms of the parasite. However, for this concentration, a quite toxicity on peritoneal macrophages was observed. For in vivo evaluation, male Wistar rats were infected with the Y strain of T. cruzi. They were orally treated with 5mg/kg body weight/day of MEL and subcutaneously with 40mg/kg body weight/day of DHEA. Treatment with MEL, DHEA and the association showed a significant reduction in the number of blood trypomastigotes during the acute phase of infection as compared to untreated animals (P<0.05). A significant increase in the number of macrophages and nitric oxide (NO) concentrations were observed during the peak of parasitemia with MEL alone or combined with DHEA. However, with DHEA alone, the highest concentration of NO was observed (P<0.05). Moreover, DHEA treatment increased TNF-alpha levels during infection (P<0.05). These results show that MEL, DHEA or the association of both reduces parasitemia during the acute phase of infection. The combined action of both hormones did not exert a synergic action on the hosts ability to fight infection, and it seems that among all treatments DHEA induces a more efficient immune response.
 
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Publishing Date
2010-03-12
 
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