Oxidative stress impairs skeletal muscle repair in diabetic rats

Alongside increased proteolysis, the inability to repair damaged skeletal muscle is a characteristic feature of uncontrolled diabetes. This study evaluates the role of oxidative stress in muscle-specific gene regulatory regions and myosin chain synthesis in streptozotocin (STZ)-induced diabetic and ZDF rats. In the gastrocnemius muscle of diabetic rats, prooxidant compounds were seen to increase while antioxidant levels fell. Myogenic regulatory factors--Myo, myogenin, and Jun D--were also reduced, and muscle enhancer factor (MEF)-1 DNA binding activity was impaired. Moreover, synthesis of muscle creatine kinase and both heavy and light chains of myosin were impaired, suggesting that oxidative stress triggers the cascade of events that leads to impaired muscle repair. Dehydroepiandrosterone has been reported to possess antioxidant properties. When it was administered to diabetic rats, in addition to an improved oxidative imbalance there was a recovery of myogenic factors, MEF-1 DNA binding activity, synthesis of muscle creatine kinase, and myosin light and heavy chains. Vitamin E administration to STZ-induced diabetic rats reverses oxidative imbalance and improves muscle gene transcription, reinforcing the suggestion that oxidative stress may play a role in diabetes-related impaired muscle repair.