Journal Article

Exercise Prevents Glucocorticoid-Induced Myocardial 4-Hydroxynonenal Production

Akin, Yesim, Akin, Senay, Hayta, Umit, Colluoglu, Inci Tugce, Gungor, Irem, Demirel, Haydar A., Guray, Umit

2025

Overview

Purpose 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. Methods 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 28 days at a 1 mg kg −1 dose, while C animals were injected with the same volume of saline subcutaneously. DE animals underwent an exercise training protocol of 60 min/day, 5 days a week, at 25 m/min −1 (0% grade) for 28 days. Left ventricular 4-HNE, Hsp72 levels, and pHsp25/Hsp25 ratio were determined by Western blot. Results 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). Conclusion 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.

• Publisher: Springer US,Springer Nature B.V
• Subject: 4-Hydroxynonenal / Adducts / Aldehydes - metabolism / Animals / Arteriosclerosis / Atherosclerosis / Cardiology / Cardiomyocytes / Cardiomyopathy / Cardiovascular diseases / Coronary artery disease / Dexamethasone / Dexamethasone - pharmacology / Female / Fitness training programs / Glucocorticoids / Glucocorticoids - pharmacology / Heart diseases / Hsp25 protein / HSP72 Heat-Shock Proteins - metabolism / Hsp72 protein / Hypertrophy / Ischemia / Medicine / Medicine & Public Health / Myocardium / Myocardium - metabolism / Oxidative stress / Oxidative Stress - drug effects / Phosphorylation / Physical Conditioning, Animal - physiology / Physical training / Protein adducts / Rats / Rats, Wistar / Reperfusion / Short Communication