MCI-186: further histochemical and biochemical evidence of neuroprotection.
The bioactivity of 3-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 U/L (n=14) in saline control to 1989 +/- 293 U/L (n= 15) in MCI 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.
Wu
T W
TW
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto Western Hospital, Canada. taiwu@hotmail.com
Zeng
L H
LH
Wu
J
J
Fung
K P
KP
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D020520:Brain Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D003402:Creatine Kinase / Q000097:blood; D003574:Cytochrome c Group / Q000378:metabolism; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D019271:Hypoxanthine / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011435:Propyl Gallate / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D014969:Xanthine Oxidase / Q000378:metabolism
D003574:Cytochrome c Group; D016166:Free Radical Scavengers; D005609:Free Radicals; D018696:Neuroprotective Agents; D019271:Hypoxanthine; D011435:Propyl Gallate; D014969:Xanthine Oxidase; D003402:Creatine Kinase; D000077553:Edaravone; D000983:Antipyrine