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Evaluation of the lysosomal autophagic process in the skeletal muscle tissue of rats submitted to supplementation of omega-3 fatty acid (EPA / DHA) associated or not with dexamethasone administration

Grant number: 17/26321-9
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): April 01, 2018
Effective date (End): March 31, 2019
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal researcher:Edmar Zanoteli
Grantee:Felipe Pereira da Silva
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Skeletal muscular atrophy can occur through numerous physiological or pathological processes of the organism, such as aging, prolonged fasting, cancer, septicemia or even by the use of glucocorticoids. Synthetic glucocorticoids are widely used in clinical practice and are one of the most common causes of drug myopathy, activating various systems of muscle degradation, mainly the proteasome and lysosomal ubiquitin systems. Several therapeutic compounds have been tested to prevent glucocorticoid-induced muscle atrophy; however, some unsuccessful ones and others such as omega-3 have been shown to be potentiators of muscle atrophy caused by glucocorticoids. Since omega-3 has been shown to potentiate lysosomal activity in other tissues, its association with dexamethasone (inducing autophagic muscle activity) could lead to a negative muscle result. OBJECTIVE: To evaluate the impact of omega-3 supplementation (EPA / DHA) on the autophagic / lysosomal system during the muscle atrophy process caused by dexamethasone in rats. METHODOLOGY: Methodologically, 60 male Wistar rats aged 10 to 12 weeks were separated into two groups (30 animals each) that received or not n-3 (100mg / kg / day) via gavage for 40 days. In the last 10 days of supplementation, 20 animals from each group received subcutaneous dexamethasone (Dx) at 2.5 or 1.25 mg / kg / day for induction of muscular atrophy, without suspending n-3 supplementation, establishing Thus 6 groups: Control; N-3; Dx1.25mg; Dx2.5mg; Dx1.25mg + n-3; And Dx2.5mg + n-3. After the experimental period the anterior tibial muscles were collected for histological analysis of acid phosphatase and protein evaluation by western blotting for expression of P-62 and LC3 1 and 2. (AU)

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