Modulação da atividade microbicida de macrófagos pela pterocarpanoquinona LQB-118 e sua ação terapêutica em modelo experimental de infecção com Leishmania (Viannia) braziliensis

• Autor(a) principal: Souza, Luciana Costa de
• Data de Publicação: 2016
• Outros Autores: [e-mail]
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/17517
• topic: Leishmania (Viannia) braziliensis; LQB-118; Macrophages; Human cell; Hamster Immunomodulation; Oral treatment; Leishmania (Viannia) braziliensis; LQB-118; Macrófagos; Célula humana; Hamster; Imunomodulação; Tratamento oral; CIENCIAS BIOLOGICAS::MICROBIOLOGIA::MICROBIOLOGIA APLICADA::MICROBIOLOGIA MEDICA

Leishmaniasis is among the leading Brazilian endemics and is among the most neglected diseases in the world. The therapeutic arsenal available is restrictive, toxic, ineffective in situ, due to emergence of resistant strains. In Brazil, there were the 20 most cases of cutaneous leishmaniasis, with one Leishmania (Viannia) braziliensis being one of the main causal forms of cutaneous and mucosal surgery. Therefore, important studies that lead to the development of new therapeutic alternatives become important. Pterocarpanoquinone LQB-118 is a molecule which exhibits antitumor activity against Trypanosoma cruzi and Leishmania species both in vitro and in vivo. The aim of this article is to study the LQB-118 synthetic modulator of movement on hamsters and human macrophages, infected or not by L. (Viannia) braziliensis. The antiparasitic effect was evaluated on in vitro growth of intracellular amastigote forms in peritoneal macrophages of hamsters and human peripheral blood. The evaluation of apoptosis using an anti-amastigote to move action, and the anti-amastigote noise is the induction of apoptosis using synchronization and anti-amastigote in action (ERO) in peritoneal macrophages of hamsters and in human macrophages of the modulating effect was directed to the measurement of nitric oxide and cytokines IL1-β, IL-6, IL-8, IL-10, IL-12 and TNF-α (by flow cytometry) in the supernatants of macrophages treated with a LQB-118 before or after an infection. The action of LQB-118 in vitro was dose-dependent inhibition of 0.8%, 75% and 88% in the combinations of 5, 10 and 20 μM, respectively for treated hamster macrophages for 48 hours post-infection. For human macrophages the inhibition was 31%, 52% and 81.5% for the concentrated conditions. In macrophages treated for 24 hours with LQB-118 prior to infection, the reduction of the hit rate was 62%, 89% and 95 in the combinations of 5, 10 and 20 μM respectively for hamster and 61% macrophage, 71 % and 79% for human macrophages in them. LQB-118 was able to induce DNA fragmentation of the intracellular amastigote forms, without altering the viability of the host cell. LQB-118 may be used to modulate macropath before or after infection. In vivo, oral treatment was able to decrease infectivity, reduce parasitic capacity and stimulate an intradermal response to total Leishmania antigens. The results showed that an anti-Leishmania activity of LQB-118 is directly related to the process of induction of death by apoptosis, and also a modulating action of the response of macrophages that contribute to the leishmanicidal action, without any change in cell viability hostess. LQB-118 may be an important molecule for the development of a new drug.