Ação do Glucantime® sobre macrófagos de camundongos

• Autor(a) principal: Siqueira, Larissa Moreira
• Data de Publicação: 2014
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/14428
• topic: Glucantime®; Macrophage; Immunomodulation; Glucantime®; Macrófagos; Imunomodulação; Gluconato de Antimônio e Sódio Uso terapêutico; Antiprotozoários Uso terapêutico; Leishmaniose; Leishmaniose Tratamento; Macrófagos; Ativação de Macrófagos Efeitos de drogas; Imunomodulação Efeitos de drogas; CNPQ::CIENCIAS BIOLOGICAS::PARASITOLOGIA::PROTOZOOLOGIA DE PARASITOS

The pentavalent antimonial drugs, such as Glucantime®, are generally used as first choice for the treatment of leishmaniasis, however its mechanism is not fully understood. It has activity against intracellular amastigotes of Leishmania sp, compromising the redox potential and causing damage to the DNA of the parasite. Some studies suggesting that Glucantime® enhances phagocytosis and TNF-α production by phagocytes. The aim of this study is to evaluate the modulation of Glucantime® on macrophages, the major host cell of Leishmania. Initially, Glucantime® s toxicity was tested on peritoneal macrophages from BALB/c mice, by treating the monolayers in vitro for 48 hours. Cell viability was evaluated by MTT method. The capacity of Glucantime® (0,1, 1 and 10 mg/ml) of modulate macrophages was evaluated by treating the monolayers of peritoneal macrophages for 24 hours before the infection with Leishmania braziliensis. After 48 hours of incubation with culture medium the infection index was evaluated by counting. Before and after the infection were analyzed the production of nitric oxide (NO) by Griess method, reactive oxygen species (ROS) by fluorimetry using the H2DCFDA dye and cytokines by ELISA. To evaluate if Glucantime® could modulate macrophages in vivo, Swiss Webster mice were treated for 5 consecutive days with 8 mg Glucantime® by intraperitoneal route. Peritoneal macrophages were evaluated about its capacity of control the in vitro infection with L. braziliensis. Results showed that until the concentration of 10 mg/ml, Glucantime® did not alter the macrophages viability in vitro. The pre-treatment of macrophages with Glucantime® at 0.1mg/mL, 1mg/mL and 10mg/mL was able to reduce the infection index in 49%, 74% and 85%, respectively. On non-infected macrophages the NO production was increased at 10mg/ml of Glucantime®. The treatment with 1 and 10 mg/ml de Glucantime® was able to significantly increase the ROS production (p<0,05 and p<0.01, respectively) and IL-12 production (p<0,05), however the IL-10 production was not altered. There were no significant changes of these parameters comparing to control after the L. braziliensis infection. The macrophages from the treated mice were capable of reduce the infection index by L. braziliensis (p<0,05). These results suggest that Glucantime® is capable of activate macrophages and this effect could contribute to the mechanism of action of this drug.