MDL 74,180 reduces cerebral infarction and free radical concentrations in rats subjected to ischaemia and reperfusion.
The protective effect of MDL 74,180 (2,3-dihydro-2,2,4,6, 7-pentamethyl-3-(4-methylpiperazino)-methyl-1-benzofuran-5-ol dihydrochloride) and alpha-tocopherol analogue free radical scavenger, against cerebral ischaemia and reperfusion in conscious rats has been demonstrated. Tissue damage following middle cerebral artery occlusion (2 h) and reperfusion (8 days) was decreased by MDL 74,180 (0.1 and 1.0 mg/kg per h) infusion beginning 15 min before the onset of reperfusion and continuing for 2 h into the reperfusion period, in a dose-related manner. Nitroxide radical adducts, characterized and quantified by electron spin resonance spectroscopy, were formed on the addition of spin traps to homogenized rat brain tissue previously subjected to global ischaemia and reperfusion. The primary oxidative chain free radicals form diamagnetic intermediates whose slow homolytic decomposition subsequently yields the observed stable spin adducts. Infusion of MDL 74,180 (1-10 mg/kg per h) beginning 15 min before the induction of global cerebral ischaemia (20 min) until the end of reperfusion (5 min), led to a dose-dependent reduction in the final concentration of spin adducts.
Cowley
D J
DJ
Marion Merrell Research Centre, Strasbourg, France.
Lukovic
L
L
Petty
M A
MA
D000818:Animals; D001572:Benzofurans / Q000627:therapeutic use*; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D002545:Brain Ischemia / Q000378:metabolism* / Q000517:prevention & control*; D002536:Cerebral Arteries / Q000502:physiology; D002544:Cerebral Infarction / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D005609:Free Radicals / Q000378:metabolism; D008297:Male; D010879:Piperazines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control*; D013113:Spin Labels
D001572:Benzofurans; D016166:Free Radical Scavengers; D005609:Free Radicals; C101402:MDL 74,180; D010879:Piperazines; D013113:Spin Labels