PKC β inhibitor ruboxistaurin prevents the increase of 15‐F2t‐isoprostane in the myocardium and plasma in Type 1 diabetic rats

Abstract

Levels of 15‐F2t‐isoprostane (IsoP), a specific marker of oxidative stress and a recently identified independent predictor of myocardial morbidity in patients with ischemic heart disease, are increased in the myocardium and plasma in Type 1 diabetes. The beta isoform of Protein kinase C (PKCβ) is over‐expressed in the myocardium of diabetic rodents and contributes to the development of diabetic cardiomyopathy and associated complications. We postulated that selective PKCâ inhibition with ruboxistaurin would attenuate hyperglycemia‐induced oxidative stress and normalize IsoP production. Control or streptozotozin‐induced diabetic rats were treated (DT) or untreated (C, D) with ruboxistaurin (1 mg/kg/day) delivered by oral gavage for four weeks. Myocardial IsoP content, cardiac mass and plasma IsoP were significantly increased while there was a significant decrease in superoxide dismutase activity in D compared to C rats (all P<0.05). Ruboxistaurin treatment normalized all these changes. It is concluded that ruboxistaurin may have prevented hyperglycemia‐induced oxidative stress by restoring endogenous antioxidant enzyme superoxide dismutase activity in diabetes.Supported by RGC/GRF grants (HKU781109M to ZX, HKU766709M to MGI) and University of Hong Kong seeding grant for basic research (ZX).