Leptospirose experimental: IgG anti-eritrócitos , alterações hemostáticas e redução da lesão renal por deferoxamina

• Autor(a) principal: Sobroza, Ânderson Oliveira
• Data de Publicação: 2016
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Manancial - Repositório Digital da UFSM
• Texto Completo: http://repositorio.ufsm.br/handle/1/17925
• topic: Leptospirose; Anemia; Trombocitopenia; Quelante; Histopatologia renal; Leptospirosis; Thrombocytopenia; Chelation; Renal histopathology; CNPQ::CIENCIAS AGRARIAS::MEDICINA VETERINARIA

Acute leptospirosis has a large part of its clinical manifestations as a function of the vascular injury with endothelial cell damage provided by the infection. Fever, jaundice, renal failure, nephritis, hemolytic anemia, hemoglobinuria, and fatal pulmonary haemorrhage are relevant clinical features. The lesion is probably due to deposits of immune complexes in the small vessels of the affected organs. The activation of the immune response determines the release of several humoral factors, generating the inflammatory process. Oxidative mechanisms are directly involved and correlate with changes in iron metabolism during disease. Kidney tissue is strongly affected by infection. However, the mechanisms involved in anemia, with or without hemolysis, thrombocytopenia related to nonclinical bleeding, and renal antioxidant pathophysiology during acute infection are poorly understood. The objective of this work was to determine, in a first experiment, the presence of immunoglobulins associated with the erythrocyte and platelet wall, to establish the magnitude of the involvement of platelet microparticles and its relation with classic laboratory hemostasis markers. For this purpose, 18 male animals were used, with 60 days divided into 2 groups (6 healthy controls and 12 infected by experimental inoculation with Leptospira interrogans Sorovar Canicola), which had blood samples collected on the 4th day after experimental infection. In a second experiment the objective was to evaluate the antioxidant and histoprotective effect of deferoxamine at renal tissue level. Also, 18 animals were submitted to the same inoculation, divided into 4 groups: C and CT (control and treated) 3 animals each, I and IT (infected and infected treated) 6 animals each. Animals of the CT and IT groups received 50mg / kg of deferoxamine on days -1, 0, 1, 2 and 3. Blood was collected and serum dosages of ferric metabolism and euthanasia were also performed on the 4th day post infection. Renal tissue was submitted to evaluation of oxidative lesion, antioxidant and inflammatory status and histopathological evaluation. Infected animals presented clinical bleeding, decreased platelet count, changes in hemostatic parameters (increase in PT, APTT, and decrease in fibrinogen), increase in platelet microparticles and increase in anti-erythrocyte IgG. Treatment with deroxamine provided reduction of renal damage assessed by TBARS, GSSH / GSSG ratio, tissue acetylcholinesterase. Histopathological evaluation measured the tissue aggression caused by the infection and pointed to protection, at the tubular level, by deferoxamine. It was possible to conclude, therefore, that the experimental infection causes important changes from the pathophysiological point of view demonstrating involvement of the immune system in the pre-hemolytic erythrocyte level and that immune-mediated factors do not seem to be correlated with thrombocytopenia. There is involvement of microparticles in the modulation of thrombotic response and, furthermore, deferoxamine presented an important antioxidant, antiinflammatory and histoprotective action in renal tissue.