An antioxidant treatment potentially protects myocardial energy metabolism by regulating uncoupling protein 2 expression in a chronic beta-adrenergic stimulation rat model.

Excessive beta-adrenergic stimulation causes cardiac toxicity, which also contributes to cardiac oxidative stress. Although uncoupling protein 2 (UCP2), a member of the mitochondrial inner membrane carrier family, can regulate energy efficiency and oxidative stress in mitochondria, little data exist regarding interactions between UCP2 expression and beta-adrenergic stimulation induced cardiac oxidative damage. We investigated whether chronic beta-adrenergic stimulation induces myocardial energy metabolism abnormality via oxidative stress, including any role of UCP2. We also examined whether 3-methyl-1-phenyl-2-pyrazolin-5-one (MIC-186; edaravone), a potent free radical scavenger, has cardioprotective effects against beta-adrenergic stimulation. Male Sprague-Dawley rats received isoproterenol (1.2 mg/kg/day) subcutaneously or/and edaravone (30 mg/kg/day) orally. Isoproterenol increased the heart/body weight ratio, accompanied by an increase in the level of myocardial thiobarbituric acid reactive substances (TBARS) and a decreased phosphocreatine (PCr) to adenosine triphosphate (ATP) ratio. Isoproterenol also markedly increased expressions of UCP2 mRNA (1.74 fold vs. non-isoproterenol) and protein (1.93 fold vs. non-isoproterenol). Edaravone had no apparent effect in hypertrophic responses, but significantly prevented both increases in TBARS and decreases in the PCr/ATP ratio. Edaravone also prevented increases in UCP2 mRNA (0.76 fold vs. isoproterenol) and protein (0.62 fold vs. isoproterenol) expressions against isoproterenol administration. Our results suggest that chronic beta-adrenergic stimulation induces myocardial energy inefficiency via excessive oxidative stress. The antioxidant effect of edaravone has potential to improve energy metabolism abnormalities against beta-adrenergic stimulation. Adequate regulation of UCP2 expression through artificial reduction of oxidative stress may play an important role in protection of the myocardial energy metabolism.