9-(4-ethoxycarbonylphenoxy)-6,7-dimethoxy-1,2,3,4-tetrahydro acridine inhibits free radical induced rat cortical neuron cytotoxicity and cerebral ischemia injury.
OBJECTIVE
To study the effects of 9-(4-ethoxycarbonylphenoxy)-6,7-dimethoxy-1,2,3,4-tetrahydro acridine (EDT) on free radical induced injury in primary cultured rat cortical neuron and cerebral ischemia in mice.


METHODS
In primary rat cortical neuron, free radical injury model was established by 10 mumol.L-1 H2O2. The content of malondiadehyde (MDA) and activity of superoxide dismutase (SOD) in cells were investigated. Chronic cerebral ischemia model was produced by occlusion of one carotid artery and pneumogastric nerve in mice. The step down test was adopted to investigate the effect of EDT on the memory impairment. The cerebra morphology and MDA, NO content and SOD activity in mice cerebra were detected.


RESULTS
In primary rat cortical culture, 0.01-3 mumol.L-1 EDT concentration-dependently inhibited the formation of MDA and reduction of SOD activity induced by 10 mumol.L-1 H2O2. In chronic cerebral ischemia, EDT 2.5, 5 and 10 mg.kg-1 ig for 5 d greatly improved the memory impairment, reduced NO efflux and MDA content, while increased SOD activity in mice cerebra.


CONCLUSIONS
EDT was found to protect neurons from H2O2-induced neurotoxicity and inhibit chronic cerebral ischemia mediated injury and memory impairment in mice.
Sheng
Rui
R
Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China. Sheng_rui@163.com
Liu
Guo-qing
GQ
D000166:Acridines / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000831:Animals, Newborn; D002545:Brain Ischemia / Q000150:complications / Q000209:etiology / Q000517:prevention & control*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D005260:Female; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000378:metabolism
C477692:9-(4-ethoxycarbonylyphenoxy)-6,7-dimethoxy-1,2,3,4-tetrahydroacridine; D000166:Acridines; D018696:Neuroprotective Agents; D009569:Nitric Oxide; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase