Protective effects of clopidogrel on oxidant damage in a rat model of acute ischemia.
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.
Kanko
Muhip
M
Department of Cardiovascular Surgery, Kocaeli University School of Medicine, Kocaeli, Turkey. muhipkanko@hotmail.com
Maral
Hale
H
Akbas
Mustafa Haluk
MH
Ozden
Meltem
M
Bulbul
Serhat
S
Omay
Oguz
O
Yavuz
Sadan
S
Berki
Kamil Turan
KT
D000818:Animals; D000077144:Clopidogrel; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism* / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control; D013482:Superoxide Dismutase / Q000378:metabolism; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology*
D016877:Oxidants; D010975:Platelet Aggregation Inhibitors; D008315:Malondialdehyde; D000077144:Clopidogrel; D013482:Superoxide Dismutase; D005978:Glutathione; D013988:Ticlopidine