Neuroprotective effect of cilostazol against focal cerebral ischemia via antiapoptotic action in rats.
This study examined the protective effects of cilostazol on cerebral infarcts produced by subjecting rats to 2-h occlusion of the left middle cerebral artery followed by 24-h reperfusion. The ischemic cerebral infarct consistently involved the cortex and striatum. The infarct size was significantly reduced, when rats received 10 mg/kg cilostazol intravenously 5 min or 1 h after the completion of 2-h ischemia. Cyclic AMP level was significantly elevated in the cortex of 4- and 12-h reperfusion (P < 0.01) following treatment with cilostazol (10 mg/kg, 5 min after 2-h ischemia) accompanied by decreased tumor necrosis factor-alpha level. Samples from the regions corresponding to the penumbra showed markedly reduced Bcl-2 protein level and, in contrast, high levels of Bax protein and cytochrome c release. Cilostazol decreased Bax protein and cytochrome c release and increased the levels of Bcl-2 protein. Cilostazol (10(-7)-10(-5) M) potently and concentration dependently scavenged hydroxyl and peroxyl radicals. In conclusion, cilostazol treatment decreases ischemic brain infarction in association with inhibition of apoptotic and oxidative cell death.
Choi
Jae Moon
JM
Department of Pharmacology, College of Medicine, and Research Institute of Genetic Engineering, Pusan National University, Pusan, Korea.
Shin
Hwa Kyoung
HK
Kim
Ki Young
KY
Lee
Jeong Hyun
JH
Hong
Ki Whan
KW
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020520:Brain Infarction / Q000473:pathology / Q000517:prevention & control; D000077407:Cilostazol; D000242:Cyclic AMP / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D016166:Free Radical Scavengers / Q000378:metabolism; D019254:Genes, bcl-2; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control; D013777:Tetrazoles / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; D003574:Cytochrome c Group; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D013777:Tetrazoles; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D000242:Cyclic AMP; D000077407:Cilostazol