Avaliação do efeito do ácido úsnico sobre o perfil redox no coração de mamíferos e em parâmetros da função cardíaca

• Ano de defesa: 2013
• Autor(a) principal: Fernandes, Valéria Alves
• Orientador(a): Santos, Sandra Lauton
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Sergipe
• Programa de Pós-Graduação: Pós-Graduação em Ciências Fisiológicas
• País: Brasil
• Palavras-chave em Português: Fisiologia; Ácido úsnico; Coração; Antioxidantes; Doença de Chagas; Usnic acid; Heart; Antioxidant; Chagas disease
• Área do conhecimento CNPq: CIENCIAS BIOLOGICAS::FISIOLOGIA
• Link de acesso: https://ri.ufs.br/handle/riufs/3996

The usnic acid AU is a secondary metabolite of lichens described as a component with antibiotic, antifungal, antiviral, anti-inflamattory, antiproliferative and antiparasitic effects. Previous studies reported that this substance has anti Tripanosoma cruzi activity. Therefore, the aim of this study was evaluate the antioxidant potential on heart, intracellular calcium dynamic and cardiac contractility effects of the usnic acid. After exposure, in vitro, to the AU, experiments were performed to assess cell viability in human endothelial cells In isolated cardiomyocytes of rats were analyzed the intracellular calcium transient, cell contractility and the production of hydrogen peroxide (H2O2), superoxide and nitric oxide (NO). After oral treatment in C57Bl6J mice with AU, were performed lipid peroxidation tests, contractility experiments (Langendorff technique), western blot to nitric oxide synthase (NOS), superoxide dismutase (SOD), glutathione peroxidase (GPx) e NADPH expressions. Enzyme kinetics was used to measure total activity of superoxide dismutase and catalase. Oral treatment with AU was performed in infected mice with Trypanosoma cruzi. The results of cell viability showed that AU was not cytotoxic, after 24 hours exposure. The cellular contractility and intracellular calcium transient were not altered after exposure in vitro to AU. Moreover, usnic acid in isolated cardiomyocytes promoted decrease in the levels of H2O2 (CTR = 564.3  72, n=88 e AU = 514,3  60, n=87), superoxide and NO superóxido (citoplasm: CTR = 231,7  42 e AU = 144,2  56,3, n=67; ***P<0,001; nuclei: CTR = 675,8  101,5 e AU = 614,2  133,4, n=60; *P<0,05) e NO (CTR = 591,8  63,7, n=85 e AU = 514,3 72,3, n=94). Oral treatment had no effect on cardiac contractility of healthy and chagasic mice. However, treatment with AU showed antioxidant, inducing decrease in lipid peroxidation (heart: CTR 0,0438  0,011 nmol MDA min-1.mg protein-1, n=9 and AU = 0,0180  0,011 nmol MDA min-1.mg protein-1, n=8. In liver CTR= 0,0145  0,021 nmol MDA min-1.mg protein1, n=8 and AU = 0,004  0,022 nmol MDA min-1.mg protein-1, n=9) and increased SOD activity in the heart and liver (CTR = 7,98  2,5 unity/g protein and AU =25, 02  4,5 unity/g protein), increased SOD and GPx expression and decreased eNOS and NADPH oxidase expression in a heart. The catalase activity showed decreased (CTR = 1,37  0,77 AE. min-1.mg protein-1 and AU = 0,45  0,22 AE. min-1.mg protein-1) and has no change in expression in a heart. The nNOS expression was not altered in a heart. In conclusion data showed suggest the AU was able to promote antioxidant effects in both experiments (in vitro and in vivo). In cardiac parameters, the AU have no changes in contract values (systolic and diastolic tension), hear rate and calcium mobility. Therefore, the AU have an antioxidant action in a heart and therapeutic potential in a Chagas disease.