Exercise Prevents Glucocorticoid-Induced Myocardial 4-Hydroxynonenal Production.

Abstract

Long-term administration of glucocorticoids (GCs) increases myocardial oxidative stress. 4-Hydroxynonenal (4-HNE) protein adducts, a marker of oxidative damage, have been associated with several cardiovascular diseases, including atherosclerosis, cardiac hypertrophy, cardiomyopathy, and ischemia-reperfusion injury. Exercise training has been shown to have a protective effect on the heart by lowering the level of oxidative stress in cardiomyocytes. Therefore, we aimed to investigate the effect of long-term dexamethasone treatment and exercise training on myocardial 4-HNE levels. Twenty-four female Wistar albino rats were assigned to sedentary control-saline treated (C, n = 8), sedentary-dexamethasone treated (D, n = 8), and exercise training-dexamethasone treated (DE, n = 8) groups. Daily dexamethasone was injected for 28days at a 1mgkg-1 dose, while C animals were injected with the same volume of saline subcutaneously. DE animals underwent an exercise training protocol of 60min/day, 5days a week, at 25m/min-1 (0% grade) for 28days. Left ventricular 4-HNE, Hsp72 levels, and pHsp25/Hsp25 ratio were determined by Western blot. The administration of dexamethasone led to a significant elevation in 4-HNE levels in the myocardium of adult rats (p < 0.05; D vs. C). The concurrent implementation of exercise training impeded this increase (p > 0.05; DE vs. C). Exercise training induced a threefold increase in myocardial Hsp72 expression (p < 0.001; DE vs. C and D) and attenuated the dexamethasone-induced increase in Hsp25 phosphorylation (p < 0.05; C vs. D) (p < 0.001; DE vs. D). Our results indicate that long-term administration of dexamethasone is associated with an increase in cardiac 4-HNE levels, which is hindered by the addition of exercise training.