Suppression of hyperemia and DNA oxidation by indomethacin in cerebral ischemia.
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.
Miyamoto
Osamu
O
Department of Neurobiology, Kagawa Medical University, 1750-1, Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
Tamae
Kazuyoshi
K
Kasai
Hiroshi
H
Hirakawa
Haruhisa
H
Hayashida
Yoshiaki
Y
Konishi
Ryoji
R
Itano
Toshifumi
T
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
D004247:DNA; D007213:Indomethacin