Protective effects of MCI-186 on cerebral ischemia: possible involvement of free radical scavenging and antioxidant actions.
Protective effects of MCI-186 on cerebral ischemia: possible involvement of free radical scavenging and antioxidant actions.
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发表时间：
1994-03
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通讯作者：
Toshiaki Watanabe;S. Yuki;M. Egawa;H. Nishi
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作者：
Toshiaki Watanabe;S. Yuki;M. Egawa;H. Nishi
本文研究了新型抗脑卒中药物3-甲基-1-苯基吡唑啉-5-酮（MCI-186）的抗脑缺血作用及其可能的作用机制。用MCI-186（3 mg/kg i.v.）MCI-186（1和3 mg/kg i.v.）还减轻了大鼠半球栓塞中的血脑屏障功能障碍和能量衰竭。用MCI-186（3mg/kg i. v.）减少大鼠局灶性栓塞中的皮质梗死。MCI-186（0.6-2.4 mM）抑制OH.诱导水杨酸的羟基化（最大抑制，40.2%），但在100 μ M，它不影响O2-的产生。MCI-186抑制由OH引起的亚油酸共轭二烯的形成。(IC50= 32.0 μ M）。此外，同时施用MCI-186（3-100 mg/kg i. v.）改善四氧嘧啶（40 mg/kg i. v.）中的高血糖症、高脂血症和β-细胞脱粒。治疗的老鼠此外，MCI-186抑制大鼠脑匀浆和线粒体匀浆中的铁依赖性过氧化（IC 50分别为15.0和2.3 μ M），并防止线粒体膜的铁依赖性过氧化分解（IC 50 = 39.0 μ M）。这些发现表明MCI-186具有有效的抗缺血作用，其机制可能与有益的抗氧化活性密切相关。
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.