Hydroxyl radical production and lipid peroxidation paralles selective post‐ischemic vulnerability in gerbil brain

Abstract

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)

Nifedipine treatment reduces brain damage after transient focal ischemia, possibly through its antioxidative effects

“…Neuronal Ca 2+ overload may trigger the formation of intracellular reactive oxygen species. 23 Moreover, hydrogen peroxide has been shown to enhance the Ca 2+ current through L-type Ca 2+ channels in cultured rat dentate granule cells. 24 The vicious circle between ischemia, Ca 2+ overload and oxidative stress may be involved in the ischemic brain damage, and cause further deterioration in the integ- Each value represents the mean ± s.e.m.…”

In VivoImaging of Reactive Oxygen Species in Mouse Brain by using [3H]Hydromethidine as a Potential Radical Trapping Radiotracer

“…A sustained increase in ROS production has been implicated in a wide variety of disease state such as inflammation, cancer, ischemia/reperfusion injury, neurodegenerative disorders, and oxidative stress. [2][3][4][5] The superoxide radical (O 2 • − ) is usually the primary ROS produced and is subsequently converted into hydrogen peroxide (H 2 8 To clarify the roles of different ROS in disease pathogenesis, highly sensitive and specific optical probes (fluorescent, luminescent, or chemiluminescent probes) for detecting ROS are being developed. [9][10][11][12] Hydroethidine, a fluorescent ROS probe, is extensively used in tissue experiments (in vitro and ex vivo) to detect O 2…”

“…Generally, a radiolabeled probe such as 3 H or 14 C is used to acquire quantitative autoradiogram with high sensitivity. Probe-labeled positron emitters such as 11 C or 18 F enable noninvasive measurement of the whole body.…”

Postischemic Application of Lipid Peroxidation Inhibitor U-101033E Reduces Neuronal Damage After Global Cerebral Ischemia in Rats

“…This is consistent with the presumed role of oxygen radical-induced lipid peroxidation in postischemic neuronal damage: As soon as reperfusion after cerebral ischemia begins, oxygen-derived free radicals, such as superoxide anion radical [27][28][29] and hydroxyl radical, 30 are generated. This is accompanied by an increase in lipid peroxidation, [31][32][33][34] which correlates with the amount of free radical generation. 35 For the 21-aminosteroid (lazaroid) tirilazad, a correlation has been demonstrated between attenuation of oxygen radical levels and/or lipid peroxidation and the neuroprotective effect.…”