Oxidative damage in fetal rat brain induced by ischemia and subsequent reperfusion. Relation to arachidonic acid peroxidation.
To determine whether ischemia followed by subsequent reperfusion can induce fetal cerebral oxidative damage, we created a model of fetal ischemia/reperfusion using rats at day 19 of pregnancy. Fetal ischemia was induced by unilateral occlusion of the utero-ovarian artery for 20 min. Reperfusion was achieved by releasing the occlusion and restoring the circulation for 30 min. The opposite uterine horn was used as control. We measured brain mitochondrial respiratory control index (RCI) and the concentration of thiobarbituric acid-reactive substances (TBARS) in each group. Arachidonic acid (AA) peroxidation induced by the incubation of brain microvessel fraction and AA was measured. AA peroxidation was also evaluated with and without aspirin, an inhibitor of cyclooxygenase and phenidone, which inhibits both of cyclooxygenase and lipoxygenase. The RCI significantly decreased by the occlusion with (p < 0.01) or without reperfusion (p < 0.05). The TBARS level significantly increased with occlusion plus reperfusion (p < 0.01). AA peroxidation was significantly greater in the occlusion and occlusion plus reperfusion groups than in the control groups (p < 0. 01). Aspirin did not affect peroxidation, while phenidone significantly inhibited it in a concentration-dependent manner (p < 0.001). Accordingly, ischemia followed by reperfusion is likely to induce fetal cerebral lipid peroxidation, which may inhibit mitochondrial respiratory activity. The phenidone-inhibited enzyme lipoxygenase may participate importantly in this peroxidation.
Department of Obstetrics and Gynecology, Kochi Medical School, Kochi, Japan.
A
A
Wakatsuki
C
C
Izumiya
Y
Y
Okatani
Y
Y
Sagara
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology; D001921:Brain / Q000098:blood supply* / Q000196:embryology* / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D005315:Fetal Diseases; D002546:Ischemic Attack, Transient / Q000150:complications*; D015227:Lipid Peroxidation; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress; D010101:Oxygen Consumption; D011247:Pregnancy; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D017392:Thiobarbituric Acid Reactive Substances; D016718:Arachidonic Acid; C015429:phenidone; D001241:Aspirin