PROTECTIVE EFFECT OF A NEW ANTIOXIDANT ON THE RAT-BRAIN EXPOSED TO ISCHEMIA-REPERFUSION INJURY - INHIBITION OF FREE-RADICAL FORMATION AND LIPID-PEROXIDATION

A new oligomeric derivative was synthesized from prostaglandin B2 and ascorbic acid, and its effect on rat brain ischemia-reperfusion injury was studied. Brain ischemia was produced in the rat by the combination of bilateral common carotid artery occlusion and hemorrhagic hypotension (30 mmHg, 20 min). The cerebral cortex was homogenized in the presence of the spin trap agent, N-tert-butyl-alpha-phenyl-nitrone (PBN). Spin-adducts were detected using an electron spin resonance spectrometer (EPR). Lipid peroxidation was estimated from the amounts of both thiobarbituric acid reactive substances (TBAR) and conjugated diene. In control experiments, reperfusion induced a burst of free radical formation which peaked at 5 min reperfusion time (238 +/- 41 %). Lipid peroxidation increased significantly after 20 min of reperfusion (TBAR, 161 +/- 50 %; conjugated diene, 160 +/-29 %). When the oligomeric derivative was administered (9 mg/kg i.p. 30 min before ischemic insult), it significantly reduced both spin adduct formation (103 +/- 13 %) and lipid peroxidation (TBAR, 109 +/- 14 %; conjugated diene, 97 +/- 33 %).