Activity of pterocarpanoquinone LQB 118 in vitro and in vivo in Leishmania braziliensis

Autor: Souza, Luciana Costa de
Přispěvatelé: Silva, Sílvia Amaral Gonçalves da, Dutra, Patrícia Maria Lourenço, Bergmann, Bartira Rossi, Santos, Eduardo Caio Torres dos
Jazyk: portugalština
Rok vydání: 2011
Předmět:
Zdroj: Biblioteca Digital de Teses e Dissertações da UERJ
Universidade do Estado do Rio de Janeiro (UERJ)
instacron:UERJ
Popis: Submitted by Boris Flegr (boris@uerj.br) on 2021-01-07T15:15:47Z No. of bitstreams: 1 Luciana Costa de Souza Dissertacao completa.pdf: 3376228 bytes, checksum: 3834798231e03c0fbd751f2d9bb2b5ec (MD5) Made available in DSpace on 2021-01-07T15:15:47Z (GMT). No. of bitstreams: 1 Luciana Costa de Souza Dissertacao completa.pdf: 3376228 bytes, checksum: 3834798231e03c0fbd751f2d9bb2b5ec (MD5) Previous issue date: 2011-04-29 The leishmaniases are among the most important endemic diseases in Brazil and are among the most neglected diseases in the world. The therapeutic tools available is restricted, toxic, expensive and ineffective in some situations, due to the emergence of resistant strains of the parasite. Are reported annually in Brazil more than 20.000 cases of cutaneous leishmaniasis and Leishmania braziliensis is the main species causing clinical forms of skin and mucosa. Therefore become important studies that lead to the development of new therapies. The aim of this study was to evaluate the activity of pterocarpanoquinona LQB118 called on Leishmania braziliensis in vitro and in vivo using hamsters as an experimental model. The antiparasitic effect was evaluated on the in vitro growth of promastigotes and on intracellular amastigotes in mouse peritoneal macrophages. To assess the mode of action in vitro was investigated using the induction of apoptosis by TUNEL labeling and Annexin V-FITC. The effect on the modulation of murine macrophage activation was assessed by measuring levels of nitric oxide (Griess reagent) and IL-12, TNF-alpha and IL-10 (ELISA) in supernatants of macrophages. In vivo therapeutic activity of LQB 118 was studied in groups of hamsters infected with L.braziliensis the paw treated with intralesional routes by LQB118 (100µM/3x/semana) or oral (0.5 mg/5x/semana) after 7 days after infection for eight weeks. The therapeutic action was analyzed using the size of the lesion. The immune response was evaluated during treatment, the response of delayed hypersensitivity (DTH) to the total antigen of L. braziliensis. The action of LQB118 in vitro was dose-dependent manner in both the promastigote inhibiting 45%, 64.7% and 99.95%, and intracellular amastigotes in 22%, 72% and 81% at concentrations of 5µM, 10µM and 20µM, respectively for both forms evolving. The LQB118 was able to induce the externalization of phosphatidylserine in promastigotes (18.57% of the cells incubated for 24 h in 25.79% of cells treated for 48h) as well promoted the increase of fluorescence in the two evolutive forms of Leishmania compared to controls, demonstrating the induction of DNA fragmentation of the parasite. This substance was also able to modulate the response of macrophages infected for 24 h increased in a dose-dependent IL-12 and NO, TNF-α was kept constant. In vivo, in the seventh week of treatment, we observed a significant reduction in lesion size in animals treated with intralesional LQB 118 (p
Databáze: OpenAIRE
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