Efeitos cardioprotetores do exercício na cardiomiopatia induzida por doxorrubicina: contribuição do óxido nítrico

• Ano de defesa: 2017
• Autor(a) principal: Sequeira, Cláudia de Morais
• Orientador(a): Matsuura, Cristiane
• Banca de defesa: Borges, Juliana Pereira , Rocha, Vinícius Novaes
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade do Estado do Rio de Janeiro
• Programa de Pós-Graduação: Programa de Pós-Graduação em Biologia Humana e Experimental
• Departamento: Centro Biomédico::Instituto de Biologia Roberto Alcantara Gomes
• País: BR
• Palavras-chave em Português: Óxido nítrico; Exercício; Doxorrubicina; Estresse oxidativo
• Palavras-chave em Inglês: Nitric oxide; Oxidative stress; Exercise; Doxorubicin
• Área do conhecimento CNPq: CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
• Link de acesso: http://www.bdtd.uerj.br/handle/1/7876

Doxorubicin (DOX) is an effective chemotherapeutic in the regression of various neoplasms, but its clinical use is limited by cardiotoxicity. Among the existing strategies to attenuate the toxic effect of the drug, physical activity has been recognized as cardioprotective; however, this relationship has not been studied. In this context, the present study was based on the hypothesis that the beneficial effect of exercise can be mediated through nitric oxide (NO), an essential inorganic gas for cardiovascular homeostasis. For this, we investigated the effects of aerobic training on the structure of cardiac tissue, synthesis of NO and biomarkers of oxidative stress in the heart of rats Sprague Dawley with heart failure induced by DOX. The effects of the exercise were also evaluated in the concomitant presence of DOX and NG-nitro-L-arginina-metil-ester (L-NAME), which inhibits NO production. Thus, the following groups were formed: (1) control (CONT); (2) DOX + exercise (DOX / EX); (3) DOX + sedentary (DOX / SED); (4) L-NAME + sedentary (L-NAME / SED); (5) DOX + L-NAME + exercise (DOX / L-NAME / EXE); And (6) DOX + L-NAME + sedentary (DOX / L-NAME / SED). The administration of doxorubicin led to a reduction in the expression of the neuronal and inducible isoforms of NO synthase (NOS), responsible for the synthesis of NO. The exercise, however, was able to reverse this change, since there was no difference between the DOX / EXE and control groups. In the evaluation of oxidative damage of lipids and proteins, no differences were observed between the groups. In relation to the activity of antioxidant enzymes, it was observed that the exercise was able to increase the activity of superoxide dismutase and catalase in animals with heart failure in relation to the DOX / SED group; and the restoration of catalase activity was not observed in the DOX / L-NAME / EXE group. The antioxidant enzyme glutathione peroxidase showed the opposite result, since its activity was higher in the DOX / SED group in relation to the others. Regarding the analysis of the cardiac structure, no hypertrophy was observed in any of the groups, on the other hand, the animals of the DOX / SED group showed an increase in interstitial fibrosis compared to controls and exercised animals that received DOX, but did not differ in relation to the group DOX / L-NAME / EXE. The results demonstrate that aerobic physical activity was effective in attenuating the damage caused by DOX to cardiac tissue, since there was an improvement in the profile of antioxidant enzymes, fibrosis, elevation of NOS, reduction of blood pressure, and a longer survival. Such benefits were not observed when exercise was associated with administration of L-NAME, which demonstrates a possible contribution of NO to the observed cardioprotection.