Tratamento com dose semelhante à terapêutica de oxandrolona durante a adolescência promove remodelamento cardíaco sem alteração da contratilidade na fase adulta em ratos Wistar

Abstract

Oxandrolone is an androgenic anabolic steroid used in clinical practice for the treatment of severe burns, trauma after major surgery, muscle loss related to acquired immune deficiency syndrome (AIDS), neuromuscular disorders, hereditary angioedema, and alcoholic hepatitis. It is used in the treatment of juvenile patients with idiopathic short stature and also growth problems due to rare diseases of genetic etiology. Several studies have shown that drug use during childhood and adolescence may negatively impact the adult phase of these individuals. This study aims to evaluate the effects of oxandrolone on cardiac contractility in prepubertal rats. The animals were distributed randomly into two groups: CON (control) and OXA (treated with oxandrolone 2.5mg / kg / day for four weeks). The hemodynamic parameters (+dP / dt max, -dP / dt min and Tau) were evaluated in the left ventricle. The heart was collected for histological analysis (H & E) and deposition of collagen (picrosirius red). The analysis of the expression of proteins related to the transient cytosolic Ca2+ (SERCA 2a and phospholamban), and the enzymes related to the antioxidant system (SOD1 and catalase) was performed by Western blot. The animals treated with OXA showed no increase in cardiac contractility and relaxation, although they showed an increase in left ventricular systolic pressure, but not characterizing a hypertensive condition. In addition, OXA promoted increased expression of SERCA-2a, phosphorylated phospholamban as well as the SERCA-2a / phospholamban ratio, while Na+ / Ca2+ (NCX) exchanger expression was not altered by treatment. Therefore, treatment with OXA for four weeks in prepubertal rats was able to promote cardiac hypertrophy but did not alter the cardiac function nor the proteins responsible for calcium handling, but the observed cardiac hypertrophy due to collagen deposition, is pathological. In conclusion, OXA does not appear to alter cardiac function, although it promotes structural and molecular changes.