Protective effects of p-nitro caffeic acid phenethyl ester on acute myocardial ischemia-reperfusion injury in rats

Abstract

Myocardial ischemia-reperfusion (IR) causes widespread cardiomyocyte dysfunction, including apoptosis and necrosis. The present study aimed to investigate the possible cardioprotective effects of p‑nitro caffeic acid phenethyl ester (CAPE-NO2) on myocardial IR‑induced injury in vivo. To generate a rat model of myocardial IR, the left anterior descending coronary artery was occluded for 30 min, followed by reperfusion for 2 h. The rats were administered either the sham treatment (the sham and IR control groups) or the therapeutic agents [the caffeic acid phenethyl ester (CAPE) and CAPE‑NO2 groups] 10 min prior to the occlusion. Myocardial IR‑induced injury is characterized by: A significant increase in the levels of myocardial enzymes, including creatine kinase, lactate dehydrogenase and aspartate transaminase; a marked increase in intercellular adhesion molecule 1 expression levels, lipid peroxidation products and inflammatory mediators; and a significant decrease in myocardial antioxidants, including catalase, total superoxide dismutase and glutathione peroxidase. In the present study, pretreatment with CAPE‑NO2 significantly ameliorated these changes, and decreased the infarct size, as compared with the IR control group (10.32±3.8 vs. 35.65±5.4%). Furthermore, western blotting demonstrated that pretreatment with CAPE‑NO2 downregulated the myocardial IR‑induced protein expression levels of B‑cell lymphoma‑2 (Bcl‑2)‑associated X protein (Bax), cleaved caspase‑3, P38 and the Bax/Bcl‑2 ratio. CAPE‑NO2 also upregulated the myocardial IR‑induced expression levels of Bcl-2, phosphoinositide-3-kinase, phosphorylated Akt and mammalian target of rapamycin. In conclusion, the results of the present study indicated that CAPE‑NO2 demonstrated improved cardioprotective effects, as compared with CAPE; therefore, CAPE‑NO2 may represent a novel approach to pharmacological cardioprotection.