Aação do extrato etanólico da casca do pequi na cardiotoxicidade por doxorrubicina em ratos

• Autor(a) principal: Moura, Léa Resende
• Data de Publicação: 2015
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Repositório Institucional da UFG
• Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/5504
• topic: Antraciclina; Estresse oxidativo; Histopatologia; Microscopia eletrônica; Metaloproteinases; TIMP; Anthracycline; Electron microscopy; Histopathology; Metalloproteinases; Oxidative; CLINICA E CIRURGIA ANIMAL::CLINICA VETERINARIA

This study aimed to evaluate the effects of pequi shell etanolic extract (PSEE) (Caryocar brasiliense), through morphological evaluation and expression of MMP2, MMP9, TIMP1 and TIMP2 proteins in the myocardium of rats with experimental acute and chronic doxorubicin (DOX) cardiotoxicity, to better understand the mechanisms involved in this disease process. Thus, two experiments were carried out. In experiment groups of acute phase, 30 Wistar rats were divided in six groups of five animals each, being Sham group (SG) water and saline; (G1) 16 mg/kg DOX and treatment with 300 mg/kg of PSEE for 17 days; (G2) 16 mg/kg of DOX and 600 mg/kg of PSEE for 17 days; (G3) 16 mg/kg of DOX and 300 mg/kg of PSEE for 10 days; (G4) 16 mg/kg of DOX and 600 mg/kg of PSEE for 10 days; and (GC) 16 mg/kg DOX. Treatment of G1 and G2 began on day one and continued until the end of the experiment, on the 17th. G3 and G4 animals were treated with PSEE for ten days, from the day seven, and DOX was applied on the 14th day after the experiment beginning. Three days after the application of DOX, on the 17th, the animals were euthanized and macroscopic evaluation and collection of samples for enzymatic analysis, histopathology and immunohistochemistry were performed. In groups of the chronic phase experiment, 30 Wistar rats were divided in six groups of five animals. G1 and G2 received 300 mg/kg and 600 mg/kg of PSEE, respectively, as pretreatment, by gavage for seven days. In G1, G2, G3, G4 and control group (CG), cardiotoxicity was induced with weekly applications of 2 mg/kg DOX, intraperitoneally, totaling four applications (8 mg/kg), and Sham group (SG) received 1 ml saline solution. G3 animals received daily 300 mg/kg of PSEE and G4, 600 mg/kg, by gavage, for 21 days of application of DOX. The CG and SG received 1 ml of water daily by gavage also. After completion of the application animals were kept for two months, totaling three months of treatment. Macroscopic evaluation was performed by the 90 days and samples were taken for analysis in electron microscopy, histopathology and immunohistochemistry. In acute experiment was concluded that PSEE attenuates the the deleterious effects of the DOX on cardiac muscle undergoing acute drug-induced cardiotoxicity. When used at doses of 300 and 600 mg/kg for 17 days PSEE attenuates vacuolar degeneration in myocytes. When used at a dose of 600 mg/kg for 10 days PSEE reduces the fibers disruption. PSEE at a dose of 300 mg/kg for 17 days increases TIMP1 expression in the myocardium of rats treated with DOX. In chronic experiment was concluded that PSEE is effective in minimizing effects of chronic cardiotoxicity induced by DOX in the myocardium of rats, whereas at doses of 300 and 600 mg/kg, PSEE attenuates vacuolar degeneration in myocytes and at the dose of 600 mg/kg the PSEE reduces the amount of Anitschkow cells and myofibrils fragmentation. Keywords: Anthracycline, electron microscopy, histopathology