Hydroxyl radical production and lipid peroxidation parallels selective post-ischemic vulnerability in gerbil brain.
The salicylate trapping method was used to investigate the changes in hydroxyl radical (.OH) levels in the selectively vulnerable hippocampus compared to the cerebral cortex of gerbils subjected to a 10 min period of near complete forebrain ischemia. Salicylate-derived 2,5-dihydroxybenzoic acid (2,5-DHBA) was measured in sham-operated animals and at 1, 5, and 15 min of reperfusion. A basal level of 2,5-DHBA was also seen in non-ischemic gerbil brain, both in the hippocampus and cortex. The hippocampal basal level was 160% higher than in the cortex (P < .01). Treatment with the cytochrome P450 inhibitor SKF-525A (50 mg/kg s.c. 30 min before measurement) did not affect this basal level in either hippocampus or cortex, which argues against a contribution of metabolic salicylate hydroxylation as its source. In contrast, pretreatment with the arachidonic acid cyclo-oxygenase inhibitor ibuprofen (20 mg/kg s.c.) decreased (-68.8%) the level of salicylate hydroxylation in the hippocampus, but not the cortex. In animals subjected to 10 min of forebrain ischemia, a selective increase in 2,5-DHBA was observed in the hippocampus at 1 min of reperfusion which subsided by 5 min. No increase in salicylate hydroxylation was apparent in the cortex within the same time frame. The increase in .OH in the hippocampus at 1 min of reperfusion was accompanied by a significant decrease (-15.7%; P < .03) in the hippocampal levels of vitamin E. No loss of vitamin E was observed in the cortex at the same time.(ABSTRACT TRUNCATED AT 250 WORDS)
Hall
E D
ED
CNS Diseases Research, Upjohn Company, Kalamazoo, Michigan 49001.
Andrus
P K
PK
Althaus
J S
JS
VonVoigtlander
P F
PF
D000818:Animals; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D065607:Cytochrome P-450 Enzyme Inhibitors; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals; D005841:Gentisates; D005849:Gerbillinae; D006624:Hippocampus / Q000378:metabolism*; D006878:Hydroxides / Q000378:metabolism*; D062385:Hydroxybenzoates / Q000378:metabolism; D017665:Hydroxyl Radical; D007052:Ibuprofen / Q000494:pharmacology; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D011335:Proadifen / Q000378:metabolism; D015424:Reperfusion; D012459:Salicylates / Q000494:pharmacology; D020156:Salicylic Acid; D014810:Vitamin E / Q000378:metabolism
D065607:Cytochrome P-450 Enzyme Inhibitors; D005609:Free Radicals; D005841:Gentisates; D006878:Hydroxides; D062385:Hydroxybenzoates; D008054:Lipid Peroxides; D012459:Salicylates; D014810:Vitamin E; D017665:Hydroxyl Radical; D011335:Proadifen; D020156:Salicylic Acid; C010925:2,5-dihydroxybenzoic acid; D007052:Ibuprofen