|Support type:||Scholarships in Brazil - Doctorate|
|Effective date (Start):||June 01, 2012|
|Effective date (End):||May 31, 2015|
|Field of knowledge:||Health Sciences - Medicine - Medical Clinics|
|Principal researcher:||Marina Politi Okoshi|
|Home Institution:||Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil|
Skeletal muscle abnormalities can contribute to reduced exercise tolerance in heart failure (HF). The mechanisms responsible for muscle abnormalities are not completely elucidated. Oxidative stress has been shown to participate in muscle changes related to aging, diabetes, and lung diseases. In this study, we test the hypothesis that HF-induced myopathy is characterized by increased oxidative stress which can be attenuated by treatment with the NADPH oxidase inhibitor apocynin. Objectives: 1) to analyze muscle phenotype and oxidative stress in the soleus muscle of rats with aortic stenosis (AS)-induced HF; and 2) to evaluate whether the treatment with apocynin attenuates or prevents increased oxidative stress and phenotypic changes. Twenty weeks after inducing AS, rats will be randomized into two groups: AS vehicle and AS treated with apocynin for eight weeks. Rats will be subjected to echocardiogram before and after the treatment. Histological analysis of soleus will be performed on NADH-TR stained sections. Antioxidant enzymes activity will be assessed by spectrophotometry. Oxidative stress in skeletal muscle will be analyzed by quantification of hydroperoxide and malondialdehyde. Total generation of reactive oxygen species will be evaluated by assessing oxidation products derived from dihydroethidium by HPLC. NADPH oxidase activity will be assessed by HPLC and fluorometry analyses of dihydroethidium oxidation products. Myosin heavy chains isoforms will be analyzed by electrophoresis. Statistical analysis: ANOVA and Bonferroni.