MCI-186 (3-Methyl-1-phenyl-2-pyrazolin-5-one) Attenuated Simulated Ischemia/Reperfusion Injury in Cultured Rat Hippocampal Cells(Pharmacology)

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概要

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• The reactive oxygen species and Ca^<2+> 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 300μM. Intracellular free calcium concentration ([Ca^<2+>]_i) was significantly reduced in the 100μM MCI-186-treated group compared to the untreated group (32.5±4.0 versus 50.2±3.6, p<0.01). Treatment with 100μM 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% (100μM MCI-186 treated group). There was no significantly protective difference between 100 and 300μM MCI-186. MCI-186 effectively protects neuron injury after simulated ischemia/reperfusion by inhibiting lipid peroxidation, reducing Ca^<2+> overload, elevating mitochondria membrane potential, and decreasing apoptosis.

• 公益社団法人日本薬学会の論文
• 2006-08-01

著者

• WANG Wei

  Department of Mechanical Engineering, Chiba University

• Wu Jin

  Department of Radiology, Institute of Clinical Medicine, University of Tsukuba

• Ding Xin-sheng

  Department Of Neurology The First Affiliated Hospital Of Nanjing Medical University

• Wu Jin

  Department Of Neurology The First Affiliated Hospital Of Nanjing Medical University

• Wu Ting

  Department Of Neurology The First Affiliated Hospital Of Nanjing Medical University

• Wu Jin

  Department Of Gastroenterological And Hepato-biliary-pancreatic Surgery Osaka City University Gradua

• Wang Wei

  Department Of General Surgery Shanghai Chang Zheng Hospital Second Military Medical University

• Wu Ting

  Department Of Chemistry East China Normal University

• Wang Wei

  Department Of Biology Graduate School Chinese Academy Of Sciences Beijing

• Wang Wei

  Department Of Neurology The First Affiliated Hospital Of Nanjing Medical University

• Wang Wei

  Department Of Biochemistry Hainan Medical College

• Wang Wei

  Department of Anesthesiology, China-Japan Friendship Hospital, the Chinese Ministry of Health, Beijing, China

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