Antioxidant N‐Acetylcysteine attenuates the reduction of cardiac Brg1 protein expression in Type1 Diabetic Rats

Abstract

Hyperglycemiainduced oxidative stress contributes to the development of diabetic cardiac complications. Brahma‐related gene 1(BRG1) is a key gene in regulating the expression of important endogenous antioxidant enzymes, including heme oxygenase‐1(HO‐1) which is central to cardioprotection, while cardiac HO‐1 is reduced in diabetes. We hypothesized that cardiac Brg1 expression is reduced in diabetes which can be restored by antioxidant treatment with N‐acetylcysteine (NAC). Control and streptozotocin‐induced diabetic rats were treated with NAC in drinking water or placebo for 4 weeks. At termination, cardiac function was assessed by echocardiography, and plasma and heart tissue free 15‐F2t‐isoprostane as well as myocardial Brg1 and HO‐1 protein expression were assessed. Plasma and cardiac free15‐F2t‐isoprostane in diabetes were increased, while cardiac Brg1 and HO‐1 protein expression were significantly decreased. Diabetes decreased the ratio of left ventricular peak velocity of early and late diastolic filling (E/A) and reduced isovolumetric relaxation time, indicative of diastolic dysfunction. NAC significantly increased cardiac Brg1 and HO‐1 protein expression and improved cardiac function. It is concluded that cardiac Brg1 is reduced in diabetes and enhancement of cardiac Brg1 may represent a novel mechanism of NAC cardioprotecion.