MCI-186: further histochemical and biochemical evidence of neuroprotection

The bioactivity of 5-methyl-1-phenyl-pyrazolin-5-one (MCI-186) was examined based on histochemical changes in drastic global ischemic rat brains. Rats with mean arterial blood pressure reduction were subjected to 60 min cerebral ischemia/80 min reperfusion. Infusion of MCI-186 at 3.0 mg/Kg reduced brain infarction from 21 +/- 4% (saline control, n=15) to 11+/-3% (n=16, p<0.05). By comparison, infusion of up to 20 mg/Kg propyl galalate (PG)- a well documented antioxidant -produced an infarct percentage of 14+/-5% (n=8), close to the saline control. Biochemically, the neuroprotective effect of MCI-186 was demonstrated by diminishing the release of creatine kinase (CK) in serum from 3363 +/- 608 Un (n=14) in saline control to 1989+/-293 Un (n=15) in MCl group (p<0.05), while PG did not lower the activity of CK significantly. MCI-186 behaves as a free radical scavenger by suppressing the formation of superoxide anion in xanthine oxidase (XO)-hypoxanthine (HP) system (p<0.05). Our data supported our contention that MCI-186 has potent anti-stroke effect with antioxidant activities. (C) 2000 Elsevier Science Inc. All rights reserved.