PPARα activation by fenofibrate protects against acute myocardial ischemia/reperfusion injury by inhibiting mitochondrial apoptosis

Peroxisome proliferator-activated receptor alpha (PPAR alpha) is highly expressed in heart, but its metabolic regulation effect in rats with myocardial ischemia/reperfusion injury is still a controversy. In this study, the cardioprotective effect of PPAR alpha activation in rats with myocardial ischemia/reperfusion injury and its relevant mechanism was investigated. Adult male Wistar rats were pretreated with fenofibrate (80 mg/kg) daily for a period of 7 days. After the treatment period, myocardial I/R injury model was made by left anterior descending coronary artery ligation for 45 min and reperfusion for 120 min. Myocardial damage was indicated by increased myocardial infarct size and serum lactate dehydrogenase and creatine kinase activities. Significant increases in myocardial cell apoptosis, malondialdehyde (MDA) level and cleaved-caspase9 protein expression level in myocardial tissue were also observed, along with reductions of PPAR alpha and uncoupling protein 2 (UCP2) mRNA levels in myocardial tissue. Impaired mitochondria were observed under electron microscopic. However, pretreatment of ischemia/reperfusion rats with fenofibrate brought the biochemical parameters and related genes expression levels to near normalcy, indicating the protective effect of fenofibrate against myocardial ischemia/reperfusion injury in rats. Histopathological findings of the heart tissues further confirmed the biochemical findings, indicating that fenofibrate confers protection against ischemia/reperfusion-induced oxidative stress in the myocardium.