MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-one) attenuated simulated ischemia/reperfusion injury in cultured rat hippocampal cells.
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 microM. Intracellular free calcium concentration ([Ca2+]i) was significantly reduced in the 100 microM MCI-186-treated group compared to the untreated group (32.5+/-4.0 versus 50.2+/-3.6, p<0.01). Treatment with 100 microM 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 microM MCI-186 treated group). There was no significantly protective difference between 100 and 300 microM 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.
Wu
Ting
T
Department of Neurology, the First Affiliated Hospital of Nanjing Medical University, China.
Ding
Xin-Sheng
XS
Wang
Wei
W
Wu
Jin
J
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D000077553:Edaravone; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*
D008315:Malondialdehyde; D000077553:Edaravone; D002118:Calcium; D000983:Antipyrine