Interação de Mycobacterium leprae, Leishmania amazonensis e Fusarium solani com macrófagos humanos: papel do óxido nítrico e derivados sintéticos de piridinas

• Ano de defesa: 2008
• Autor(a) principal: Vieira, Rodrigo Tonioni
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Programa de Pós-graduação em Patologia; Patologia
• Palavras-chave em Português: Macrófagos; Mycobacterium leprae; Leishmania amazonensis; Fusarium solani; Óxido nítrico; Piridinas; Derivados; MEDICINA; PATOLOGIA INVESTIGATIVA; Leishmania mexicana; CNPQ::CIENCIAS DA SAUDE::MEDICINA::ANATOMIA PATOLOGICA E PATOLOGIA CLINICA
• Link de acesso: https://app.uff.br/riuff/handle/1/18290

Microorganisms are been lived with human beings in relationships which range from symbiosis to parasitism. The mechanisms of these actions as well as the forms to affect them are still today a strong target of studying. Biopathogens as Mycobacterium leprae, Leishmania amazonensis and Fusarium solani are ethiologic agents of some chronicinfectious diseases as Leprosy, Cutaneous Leishmaniasis (CL) and Fusariosis, respectively, which affect several areas in the world. Thus, these biopathogens are subject of investigation of these relationships. The aims of the present work are: (1) to investigate the interaction of M. leprae, L. amazonensis and F. solani with human macrophages, emphasing the relevance of NO in the process of infection; the secretion of cytokines as TNF-a, TGF-β and IL-10; as well as possible morphological alterations displayed by the host cell; and (2) to investigate the effect of derivates of 5--(4,5-diidro-1H-imidazol-2-il)-4-(phenylamino)thieno[2,3-b]pyridine in the proliferation of L. amazonensis, in order that new drugs for the treatment of CL can be identified. So, the first part of this work related to the study of Nitric Oxide (NO) as efector agent of the killing of biopathogens which cause cutaneous lesions in the host, was made by using imunoenzimatic assays (ELISA). And the morphological analyses of the proccess of infection were done through Optical Microscopy (OM) and Transmission Electronic Microscopy (TEM). In the second part of this work related to the search of new drugs with potential specifically antileishmanial, without citotoxity for the host cell, the assays were done with L. amazonensis in the promastigote form, incubated in the presence of piridines derivates and analysed by OM. Similar experiments were done by using human macrophages to test the citotoxicity. Glucantime was used as control in all assays. The results concerning to the first part of this work showed the endocytosis of M. leprae, L. amazonensis and F. solani by human macrophages as observed by OM. However, in the presence of the inhibitor of NO-synthase (L-NAME), the production of NO was inhibited and, consequently, the mainteance of these biopathogens inside macrophage was increased. These results were the first experimental evidence of the relevance of NO as effective factor to permit the maintenance of M. leprae, L. amazonensis and F. solani inside human macrophage. The MET analyses confirms the results obtained with the OM, by showing details of the M. leprae in the endocytic vacuole inside the macrophage. Our results suggest the importance of NO in the process of infection of human macrophage by M. leprae, L. amazonensis and F. solani. Furthermore, high levels of TNF-α, TGF-β and IL-10 production were detected by the macrophages infected by these biopathogens. The results concerning to the second part of this work showed that the growth of L. amazonensis was inhibit by all tested compounds. However, the highest inhibitor effect of L. amazonensis growth was observed when this parasite was incubated with the 3c and 3e compounds displaying the p-CH3 and p-OCH3 groups respectively and, showing a very low citotoxicity for the human macrophages compared to the glucantime. The development of new drugs through the racional design of new drugs, by using chemicals - derived of 5-(4,5-diidro-1H-imidazol-2--il)-4-(fenilamino)tieno[2,3-b]piridine as new alternatives for the treatment of CL may be quite promising according to the results obtained here. Thus, the piridines derivated might be potentials candidates for the development of new forms of treatment of CL