title: The Effects of Xanthine Oxidoreductase Inhibitors on Oxidative Stress Markers following Global Brain Ischemia Reperfusion Injury in C57BL/6 Mice.
abstract: We demonstrated that 3-nitrotyrosine and 4-hydroxy-2-nonenal levels in mouse brain were elevated from 1 h until 8 h after global brain ischemia for 14 min induced with the 3-vessel occlusion model; this result indicates that ischemia reperfusion injury generated oxidative stress. Reactive oxygen species production was observed not only in the hippocampal region, but also in the cortical region. We further evaluated the neuroprotective effect of xanthine oxidoreductase inhibitors in the mouse 3-vessel occlusion model by analyzing changes in the expression of genes regulated by the transcription factor nuclear factor-kappa B (including pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), matrix metalloproteinase-9 and intercellular adhesion molecules-1). Administration of allopurinol resulted in a statistically significant decrease in IL-1β and TNF-α mRNA expression, whereas febuxostat had no significant effect on expression of these genes; nevertheless, both inhibitors effectively reduced serum uric acid concentration. It is suggested that the neuroprotective effect of allopurinol is derived not from inhibition of reactive oxygen species production by xanthine oxidoreductase, but rather from a direct free-radical-scavenging effect.
authors.affiliation: Nippon Medical School, Emergency and Critical Care Medicine, Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamaguchi
authors.affiliation: Nippon Medical School, Biochemistry and Molecular Biology, Tokyo, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Nippon Medical School, Biochemistry and Molecular Biology, Tokyo, Japan.
authors.forename: Teruo
authors.initials: T
authors.lastname: Kusano
authors.affiliation: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Department of Pathology, Tokyo, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Matsuda
authors.affiliation: Nippon Medical School, Emergency and Critical Care Medicine, Tokyo, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Suzuki
authors.affiliation: Nippon Medical School, Emergency and Critical Care Medicine, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Fuse
authors.affiliation: Nippon Medical School, Emergency and Critical Care Medicine, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yokota
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002545:Brain Ischemia / Q000097:blood / Q000378:metabolism*; D004195:Disease Models, Animal; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000097:blood / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014527:Uric Acid / Q000097:blood; D014968:Xanthine Dehydrogenase / Q000037:antagonists & inhibitors*
chemical_list: D000447:Aldehydes; D015415:Biomarkers; D053583:Interleukin-1beta; D016328:NF-kappa B; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D014527:Uric Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D000493:Allopurinol; D014968:Xanthine Dehydrogenase; D020780:Matrix Metalloproteinase 9; C027576:4-hydroxy-2-nonenal