Ischemic preconditioning in the rat hippocampus increases antioxidant activities but does not affect the level of hydroxyl radicals during subsequent severe ischemia.
Several studies have demonstrated that ischemic preconditioning increases superoxide dismutase activity, but it is unclear how ischemic preconditioning affects events downstream of hydrogen peroxide production during subsequent severe ischemia and reperfusion in the hippocampus. To answer this question, we investigated whether ischemic preconditioning in the hippocampal CA1 region increases the activities of antioxidant enzymes glutathione peroxidase and catalase, resulting in a decrease in the level of hydroxyl radicals during subsequent severe ischemia-reperfusion. Transient forebrain ischemia was induced by four-vessel occlusion in rats. Ischemic preconditioning for 3 min or a sham operation was performed and a 15-min severe ischemia was induced three days later. Ischemic preconditioning preserved the CA1 hippocampal neurons following severe ischemia. The concentration of 2,3-dihydroxybenzoic acid, an indicator of hydroxyl radical, was measured using in vivo microdialysis technique combined with HPLC. The ischemia-induced increase in the ratio of 2,3-dihydroxybenzoic acid concentration relative to baseline did not differ significantly between preconditioned and control groups. On the other hand, activities of the antioxidant enzymes glutathione peroxidase-1 and catalase were significantly increased at 3 days after ischemic preconditioning in the hippocampus. Our results suggest that, in preconditioned rats, while hydrogen peroxide is generated from severe ischemia, the activity of catalase and glutathione peroxidase-1 is correspondingly increased to eliminate the excessive hydrogen peroxide. However, our results show that the enhanced activity of these antioxidant enzymes in preconditioned rats is not sufficient to decrease hydroxyl radical levels during subsequent severe ischemia-reperfusion.
Choi
Yun-Sik
YS
Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
Cho
Kyung-Ok
KO
Kim
Eun-Jeong
EJ
Sung
Ki-Wug
KW
Kim
Seong Yun
SY
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D004789:Enzyme Activation; D005979:Glutathione Peroxidase / Q000378:metabolism; D006624:Hippocampus / Q000098:blood supply*; D006861:Hydrogen Peroxide / Q000378:metabolism; D062385:Hydroxybenzoates / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D019194:Ischemic Preconditioning; D008297:Male; D016548:Prosencephalon; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control; D000094765:Glutathione Peroxidase GPX1
D000975:Antioxidants; D062385:Hydroxybenzoates; D017665:Hydroxyl Radical; C009135:2,3-dihydroxybenzoic acid; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722069:Gpx1 protein, rat