Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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MCI-186 (3-Methyl-1-phenyl-2-pyrazolin-5-one) Attenuated Simulated Ischemia/Reperfusion Injury in Cultured Rat Hippocampal Cells
Ting WuXin-Sheng DingWei WangJin Wu
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2006 Volume 29 Issue 8 Pages 1613-1617

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Abstract

The reactive oxygen species and Ca2+ overload play a critical role in ischemia/reperfusion (I/R) injury. MCI-186 has potent effects in the brain as a free radical scavenger in ischemia-reperfusion. Acute glucose–oxygen deprivation and subsequent reoxygenation were used to model ischemia/reperfusion injury in cultured hippocampal cells. MCI-186 reduced malondialdehyde level and raised the SOD activity when applied upon reoxygenation in a dose-dependent manner compared with the untreated group. The peak neuroprotective effects occurred at 100 and 300 μM. Intracellular free calcium concentration ([Ca2+]i) was significantly reduced in the 100 μM MCI-186-treated group compared to the untreated group (32.5±4.0 versus 50.2±3.6, p<0.01). Treatment with 100 μM MCI-186 significantly inhibited the decrease of mitochondria membrane potential after simulated ischemia/reperfusion (204±11.6% compared with the untreated group, p<0.01). Cell apoptotic rate was significantly decreased following MCI-186 treatment from 33.7±2.3% (untreated group) to 16.6±1.4% (100 μM MCI-186 treated group). There was no significantly protective difference between 100 and 300 μM MCI-186. MCI-186 effectively protects neuron injury after simulated ischemia/reperfusion by inhibiting lipid peroxidation, reducing Ca2+ overload, elevating mitochondria membrane potential, and decreasing apoptosis.

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© 2006 The Pharmaceutical Society of Japan
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