Tohoku J. Exp. Med., 2005, 205(2)

Protective Effects of Clopidogrel on Oxidant Damage in A Rat Model of Acute Ischemia

MUHIP KANKO, HALE MARAL,¹ MUSTAFA HALUK AKBAS, MELTEM OZDEN,¹ SERHAT BULBUL, OGUZ OMAY, SADAN YAVUZ and KAMIL TURAN BERKI

Departments of Cardiovascular Surgery, and ¹Biochemistry,
Kocaeli University School of Medicine, Kocaeli, Turkey

Reperfusion injury is a consequence of inadequate energy supply and acidosis in ischemic tissues and a chain of events triggered by oxygen-derived free radicals released in response to exposure of oxygen. In this study, we aimed to assess the effects of clopidogrel, an antithrombotic agent, on experimental ischemia-reperfusion model in rats. The ischemia was performed by blockade of the circulation of right lower extremity at trochanter major level for 6 hours. Then, the extremity was reperfused for 4 hours. Another group of rats pretreated with clopidogrel (0.2 mg/kg/day) for 10 days prior to ischemia-reperfusion. After the reperfusion period, all rats were anesthetized with ketamine. Blood and tissue samples from the gastrocnemius muscle, liver and lungs were taken for the measurement of malondialdehyde (MDA), glutathione (GSH) levels and superoxide dismutase (SOD) activity. The results revealed that clopidogrel prevented the increase in MDA level and the decrease in GSH level and SOD activity caused by ischemia-reperfusion both in tissue samples and plasma. These findings suggest that clopidogrel is beneficial in prevention of ischemia-reperfusion injury probably via its effects on inflammatory cells, platelets, and endothelial cells.

keywords —— oxidant; lipid peroxidation; ischemia-reperfusion; clopidogrel

© 2005 Tohoku University Medical Press

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Address for reprints: Dr. Muhip Kanko, Kocaeli Üniversitesi Tip Fakültesi, Kardiyovasküler Cerrahi Ab.D., Kocaeli, Turkey.

e-mail: muhipkanko@hotmail.com