Effect of 21-aminosteroid lipid peroxidation inhibitor, U74006F, in the rat middle cerebral artery occlusion model.
The aim of this study was to evaluate the effect of 21-aminosteroid lipid peroxidation inhibitor, U74006F, on ischaemic brain tissue damage using the rat middle cerebral artery occlusion model. Under anaesthesia, the left middle cerebral artery was exposed without cutting the dura mater via a subtemporal craniotomy, under an operating microscope. Photo-illumination (wave length; 540 nm) was applied to the middle cerebral artery and then rose bengal (20 mg/kg) was administered intravenously. The middle cerebral artery was completely occluded by thrombus about 6 min after the administration of rose bengal. U74006F (1.0 mg/kg) was then injected intravenously just after the cessation of illumination. Twenty four hours after the operation, the extent of ischaemic damage was measured by magnetic resonance imaging technique. After measuring the extent of ischaemic damage, the brain was immediately removed from animals treated with or without U74006F for determination of lipid peroxidation, and the generation of free arachidonic acid in the brain. U74006F significantly (P < 0.01) reduced the size of ischaemic damage. Twenty-four hours after the operation, lipid peroxidation and the concentration of free arachidonic acid in the left hemisphere (infarction side) were significantly (P < 0.05) higher than in the right hemisphere. U74006F significantly (P < 0.05) decreased the content of lipid peroxidation products and free arachidonic acid. There was a significant (P < 0.05) correlation between the extent of ischaemic damage and the concentration of lipid peroxidation products in the left hemisphere 24 h after the operation. In conclusion, U74006F might reduce the extent of ischaemic damage by inhibiting lipid peroxidation in the brain, thus minimizing oxidative damage to neural tissues.
Umemura
K
K
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Wada
K
K
Uematsu
T
T
Mizuno
A
A
Nakashima
M
M
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D016166:Free Radical Scavengers; D015227:Lipid Peroxidation / Q000187:drug effects*; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors*; D008279:Magnetic Resonance Imaging; D008297:Male; D011281:Pregnatrienes / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013927:Thrombosis / Q000503:physiopathology
D016166:Free Radical Scavengers; D008054:Lipid Peroxides; D011281:Pregnatrienes; D017382:Reactive Oxygen Species; D016718:Arachidonic Acid; C053355:tirilazad