Lack of antiapoptotic effects of antiplatelet drug, aspirin and clopidogrel, and antioxidant, MCI-186, against focal ischemic brain damage in rats.
OBJECTIVE
This study evaluated the antiapoptotic effect of antiplatelet drugs, aspirin and clopidogrel, and the antioxidant drug, MCI-186, against focal cerebral ischemic rat brain damage.


METHODS
Cerebral ischemia was mechanically induced by 2-hour occlusion of the left middle cerebral artery (MCA) using an intraluminal filament followed by 24-hour reperfusion.


RESULTS
The cerebral infarct size was little affected by oral administration of 300 mg/kg aspirin, 30 mg/kg clopidogrel or 100 mg/kg MCI-186, but was significantly reduced by 30 mg/kg cilostazol. However, intravenous administration of 10 mg/kg MCI-186 suppressed the infarct size. DNA fragmentation observed in the cortical tissues corresponding to the penumbral zone was not suppressed by aspirin, clopidogrel or MCI-186, but was significantly suppressed by cilostazol. Increased phosphorylation of phosphatase and tensin homolog deleted from chromosome 10 (PTEN) and Bax protein, and decreased Akt/cyclic AMP response element binding protein (CREB) phosphorylation, including Bcl-2 protein in the vehicle-treated group were not affected by treatment with aspirin, clopidogrel and MCI-186, whereas those effects were reversed by cilostazol.


CONCLUSIONS
Thus, it is suggested that antiplatelet drugs, aspirin and clopidogrel, and antioxidant drug, MCI-186, showed little antiapoptotic effect in contrast to cilostazol.
Department of Pharmacology, College of Medicine, Pusan National University, Busan, Korea.
Jeong Hyun
JH
Lee
So Youn
SY
Park
Won Suk
WS
Lee
Ki Whan
KW
Hong
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use*; D015153:Blotting, Western / Q000379:methods; D001929:Brain Edema / Q000188:drug therapy / Q000378:metabolism; D002545:Brain Ischemia / Q000150:complications; D002544:Cerebral Infarction / Q000517:prevention & control; D000077144:Clopidogrel; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004185:Disability Evaluation; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D000077553:Edaravone; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000187:drug effects; D002534:Hypoxia, Brain / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D051028:bcl-2-Associated X Protein
D000975:Antioxidants; C494828:Bax protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein; D000077144:Clopidogrel; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; D013988:Ticlopidine; D001241:Aspirin; D000077553:Edaravone; D000983:Antipyrine