Antagonistic effect of 3,6-dimethamidodibenzopyriodonium gluconate on lipid peroxidation in cerebral cortical neuronal cultures and rat brains during focal cerebral ischemia reperfusion.
OBJECTIVE
To study 3,6-dimethamidodibenzopyriodonium gluconate (I-93) antagonistic effects on lipid peroxidation in cerebral cortical neuronal cultures and rat brains during focal cerebral ischemia-reperfusion.


METHODS
Cerebral cortical neurons were cultured and rat focal cerebral ischemia-reperfusion model was established by reversible middle cerebral artery occlusion (MCAO) without craniectomy. The efflux of lactate dehydrogenase (LDH) from neurons, content of malondialdehyde (MDA) in neurons and brain homogenate, activity of superoxide dismutase (SOD) in brain homogenate, and index of cerebral edema as well as brain morphology were investigated.


RESULTS
I-93 10-40 mumol.L-1 concentration-dependently inhibited efflux of LDH and elevated levels of MDA induced by addition of H2O2(10 mumol.L-1) in vitro. I-93 0.5 mg.kg-1 improved the cerebral morphology, reduced brain edema, decreased MDA content, and enhanced SOD activity in brain homogenate.


CONCLUSIONS
I-93 protects neurons from H2O2-induced neurotoxicity and ischemia-reperfusion mediated damage by increasing the activity of antioxidant enzymes and suppressing the generation of lipid peroxides.
Deng
X L
XL
Department of Pharmacology, China Pharmaceutical University, Nanjing 210009. qianzhiy@mailbox.cpu.edu.cn
Qian
Z Y
ZY
Liu
N F
NF
Ma
X Y
XY
Wang
H F
HF
Hou
Z J
ZJ
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D001929:Brain Edema / Q000209:etiology; D002545:Brain Ischemia / Q000209:etiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D005260:Female; D005942:Gluconates / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D005942:Gluconates; D018696:Neuroprotective Agents; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase