Protective effects of MCI-186 on cerebral ischemia: possible involvement of free radical scavenging and antioxidant actions.

Abstract

The anti-ischemic effects and a possible mechanism of a new antistroke agent, 3-methyl-1-phenyl-pyrazolin-5-one (MCI-186), were studied. Preischemic treatment with MCI-186 (3 mg/kg i.v.) facilitated the recovery of electrocorticographic activity and prolonged survival time in global complete ischemia of rats; MCI-186 (1 and 3 mg/kg i.v.) also mitigated dysfunction of the blood-brain barrier and energy failure in hemispheric embolization of rats. Postischemic treatment with MCI-186 (3 mg/kg i.v.) decreased cortical infarction in focal embolization of rats. MCI-186 (0.6-2.4 mM) inhibited the OH.-induced hydroxylation of salicylate (maximal inhibition, 40.2%), but at 100 microM it did not influence O2- generation. MCI-186 inhibited the formation of linoleic acid-conjugated dienes caused by OH. (IC50 = 32.0 microM). Also, concurrent administration of MCI-186 (3-100 mg/kg i.v.) ameliorated hyperglycemia, hyperlipopeoxidemia and degranulation of beta-cells in alloxan (40 mg/kg i.v.)-treated rats. In addition, MCI-186 inhibited iron-dependent peroxidation in rat brain homogenates and mitochondrial homogenates (IC50 = 15.0 and 2.3 microM, respectively) and prevented iron-dependent peroxidative disintegration of mitochondrial membranes (IC50 = 39.0 microM). These findings suggest that MCI-186 has potent anti-ischemic actions and that its mechanism may be closely associated with beneficial antioxidant activities.

• Authors: T Watanabe, S Yuki, M Egawa, H Nishi
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 268 Issue 3 Pg. 1597-604 (Mar 1994) ISSN: 0022-3565 [Print] United States
• PMID: 8138971 (Publication Type: Journal Article)

Chemical References

• Antioxidants
• Free Radical Scavengers
• Superoxides
• Hydroxyl Radical
• Alloxan
• Edaravone
• Antipyrine

Topics

• Alloxan
• Animals
• Antioxidants (therapeutic use)
• Antipyrine (analogs & derivatives, therapeutic use)
• Brain (blood supply, drug effects, metabolism)
• Brain Ischemia (prevention & control)
• Edaravone
• Embolization, Therapeutic
• Energy Metabolism (drug effects)
• Free Radical Scavengers
• Hydroxyl Radical
• Islets of Langerhans (drug effects)
• Lipid Peroxidation
• Male
• Mitochondria (drug effects, metabolism)
• Rats
• Rats, Wistar
• Regional Blood Flow (drug effects)
• Superoxides