IngentaConnect Lack of antiapoptotic effects of antiplatelet drug, aspirin and c...

Authors: Lee, Jeong Hyun¹; Park, So Youn¹; Lee, Won Suk¹; Hong, Ki Whan¹

Source: Neurological Research, Volume 27, Number 5, July 2005 , pp. 483-492(10)

Abstract:

Objectives: 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.

Conclusion: Thus, it is suggested that antiplatelet drugs, aspirin and clopidogrel, and antioxidant drug, MCI-186, showed little antiapoptotic effect in contrast to cilostazol.

Keywords: FOCAL CEREBRAL ISCHEMIA; ASPIRIN; CLOPIDOGREL; MCI-186; CILOSTAZOL

Document Type: Research article

DOI: 10.1179/016164105X17134

Affiliations: 1: Department of Pharmacology, College of Medicine, Pusan National University, Busan, Korea

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Lack of antiapoptotic effects of antiplatelet drug, aspirin and clopidogrel, and antioxidant, MCI-186, against focal ischemic brain damage in rats