title: Alpha-lipoic acid protects against myocardial ischemia/reperfusion injury via multiple target effects.
abstract: 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 2h 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.
authors.affiliation: Department of Toxicology, School of Preventive Medicine, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.forename: Lin
authors.initials: L
authors.lastname: Ji
authors.forename: Xin
authors.initials: X
authors.lastname: Liang
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Chun-Xu
authors.initials: CX
authors.lastname: Hai
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis; D015153:Blotting, Western; D002374:Catalase / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D005978:Glutathione; D008297:Male; D017202:Myocardial Ischemia / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D008063:Thioctic Acid / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000975:Antioxidants; D008063:Thioctic Acid; D002374:Catalase; D003402:Creatine Kinase; D005978:Glutathione