title: Suppression of hyperemia and DNA oxidation by indomethacin in cerebral ischemia.
abstract: We investigated antioxidative activity and the effect of indomethacin, an agent that inhibits cyclooxygenase, on extracellular glutamate and cerebral blood flow in cerebral ischemia in gerbils. Pre-ischemic administration of indomethacin (5 mg/kg, i.p.) significantly rescued hippocampal CA1 neurons (9+/-6 cells/mm in the ischemia, 87+/-43 cells/mm in the indomethacin group, P<0.001). DNA fragmentation induced by ischemia was also examined using the terminal deoxynucleotidyl transferase-mediated UTP nick end labeling (TUNEL) method and indomethacin reduced TUNEL positive cells (140+/-21 in the ischemia, 99+/-31 in the indomethacin group, P<0.01). In addition, indomethacin attenuated the increase in hippocampal blood flow during reperfusion, but not increased extracellular glutamate by ischemia. Eight-hydroxydeoxyguanosine (8-OH-dG), a highly sensitive marker of DNA oxidation, was measured 90 min following ischemia using high-pressure liquid chromatography. Indomethacin significantly decreased the level of ischemia-induced 8-OH-dG in the hippocampus (P<0.05). These results suggest that indomethacin may protect neurons by attenuating oxidative stress and reperfusion injury in ischemic insult.
authors.affiliation: Department of Neurobiology, Kagawa Medical University, 1750-1, Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Miyamoto
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Tamae
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kasai
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Hirakawa
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Hayashida
authors.forename: Ryoji
authors.initials: R
authors.lastname: Konishi
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Itano
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004247:DNA / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects* / Q000502:physiology; D005849:Gerbillinae; D006940:Hyperemia / Q000188:drug therapy* / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology
chemical_list: D004247:DNA; D007213:Indomethacin