Alpha-lipoic acid protects against myocardial ischemia/reperfusion injury via multiple target effects

Myocardial ischemia/reperfusion (MI/R) is a major cause for the events of cardiovascular disease. Oxidative stress plays a critical role in the development of ischemia/reperfusion (IR) injury. As a potent antioxidant, alpha-lipoic acid (LA) has been shown to provide a benefit for the inhibition of IR injury and inhibit reactive oxygen species (ROS) generation during MI/R in rats. However, the mechanism on the protective effect of LA is still to be clarified. The present study was aimed to investigate the protective effect of LA against MI/R injury and its mechanisms. We found that 2 h of myocardial ischemia followed by different time periods of reperfusion resulted in significant increase of creatine kinase (CK) activity. MI/R also significantly promoted oxidative stress and decreased the activities of antioxidant enzymes. In addition, apoptosis and inflammatory response were activated and aggravated in a time-dependent manner by MI/R. All these alterations induced by MI/R were attenuated by the administration of LA 30 min before reperfusion. These results suggested that LA played a protective effect against MI/R injury via antioxidant, anti-apoptotic and anti-inflammatory effects. These findings may significantly better the understanding of the pharmacological actions of LA and advance therapeutic approaches to MI/R injury and cardiovascular diseases.