Evaluation of ceramide in heart failure-induced skeletal myopathy

• Grant number: 19/17945-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2020
• End date: April 30, 2021
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Marina Politi Okoshi
• Grantee: Ingrid de Freitas Tosta
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Heart failure induces fatigue and dyspnea. The symptoms are caused not only by cardiovascular and pulmonary abnormalities, but also by skeletal muscle changes, which have been extensively reported in cardiac failure and named heart failure-induced skeletal myopathy. More recently, the metabolism of sphingolipids has emerged as an important feature of muscular biology. Ceramide is associated with several deleterious effects, such as muscle glucose uptake impairment, apoptosis induction, mitochondrial dysfunction, muscle cells contractile disturbance, and increased production of reactive oxygen species. The increased oxidative stress intensifies inflammatory processes leading to increased ceramide generation and the formation of a vicious cycle. Although ceramide actions suggest its involvement in conditions of muscle mass reduction, there are few reports in this subject. Since sphingolipids are abundant in skeletal muscle, their better understanding can help to identify strategies to preserve and/or recover skeletal muscle of patients with diseases related to muscle mass loss. In this study, we will test the hypothesis that ceramide is increased in skeletal muscle during heart failure and associated with increased oxidative stress and muscle atrophy. The aim of this study is to evaluate the content of ceramide and its association with increased oxidative stress and skeletal muscle atrophy in rats with myocardial infarction-induced heart failure. We will also evaluate the effects of the long-term treatment with the antioxidant N-acetylcysteine on the prevention or attenuation of muscle changes associated with heart failure. Specific objectives include the evaluation of the following parameters in soleus muscle: content of ceramide; activity of the antioxidant enzymes catalase, glutathione peroxidase, and superoxide dismutase; concentration of the oxidative stress marker lipid hydroperoxide; and cross-sectional area. (AU)