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Annals of Clinical & Laboratory Science 35:440-448 (2005)
© 2005 Association of Clinical Scientists

In Vivo Effects of Caffeic Acid Phenethyl Ester on Myocardial Ischemia-Reperfusion Injury and Apoptotic Changes in Rats

Kerim Cagli1, Cahit Bagci2, Mukaddes Gulec3, Beyhan Cengiz2, Omer Akyol4, Ibrahim Sari5, Sevgi Cavdar2, Sadrettin Pence2 and Hakan Dinckan6
1 Division of Cardiovascular Surgery, Yuksek Ihtisas Hospital, Ankara, Turkey; 2 Departments of Physiology, 5 Pathology and 6 Cardiology, Gaziantep University Medical Faculty, Gaziantep, Turkey; 3 Division of Biochemistry, Akyurt State Hospital, Ankara, Turkey; and 4 Department of Biochemistry, Hacettepe University Medical Faculty, Ankara, Turkey

Omer Akyol, M.D., Ph.D., Hacettepe University Medical Faculty, Department of Biochemistry, 06100 Sihhiye, Ankara, Turkey; tel 90 312 3051652 (x116); fax 90 312 3100580; e-mail oakyol{at}hacettepe.edu.tr.

Ischemia/reperfusion (I/R) has been reported to induce apoptotic cellular death in myocardium. This study tested the hypothesis that caffeic acid phenethyl ester (CAPE), one of the active components of propolis, may ameliorate myocardial apoptosis and oxidative myocardial injury. Wistar rats were divided into 4 groups: (i) sham operated, (ii) I/R, (iii) I/R+CAPE, and (iv) I/R+glutathione (GSH). CAPE (10 µmol/kg) was infused iv 10 min before occlusion of the left anterior descending coronary artery (30 min) followed by reperfusion (120 min). GSH (5 mg/kg) was infused iv after the occlusion and immediately before reperfusion. The TdT-mediated in situ nick end-labeling (TUNEL) method was used to evaluate apoptotic activity. I/R resulted in myocardial apoptosis, alterations of antioxidant status, elevation of serum creatine kinase (CK) and aspartate aminotransferase (AST) activities, evidence of lipid peroxidation, and elevated nitric oxide levels, compared to the sham-operation group. No apoptotic cells were found in the myocardial tissue of sham-operated rats. The TUNEL-positive myocardial cells averaged 60%, 30%, and 40% in the I/R, I/R+CAPE, and I/R+GSH groups, respectively. This study demonstrates that pretreatment with CAPE provides cardio-protection from I/R injury. The I/R+CAPE group showed reduced apoptosis, attenuated NO production, elevated myocardial superoxide dismutase (SOD) activity, and diminished serum CK and AST activities, compared to the I/R group.

Keywords: caffeic acid phenethyl ester, myocardial ischemia/reperfusion injury, apoptosis




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