title: Stable nitroxide Tempol ameliorates brain injury by inhibiting lipid peroxidation in a rat model of transient focal cerebral ischemia.
abstract: Oxygen free radicals have been implicated in the pathogenesis of cerebral ischemia and reperfusion injury. 4-Hydroxy-2,2,6,6-tetramethylpiperidene-1-oxyl (Tempol) has been reported as a stable nitroxide and a membrane-permeable free radical scavenger. This study was performed to investigate the mechanism of Tempol in attenuating ischemia-reperfusion injury in a rat model of transient focal cerebral ischemia. We measured the cerebral 2,3-dihydroxybenzoic acid (DHBA) level as the amount of hydroxyl radical production using a microdialysis technique with salicylic acids trapping during ischemia and reperfusion. The concentration of cerebral thiobarbituric acid reactive substances (TBARS), representing the extent of lipid peroxidation by free radicals, and the area of cerebral infarction were also measured. The level of cerebral 2,3-DHBA was increased during ischemia and reperfusion, especially during the early reperfusion stage at the periphery of the infarct area (nearly 500-fold). Intravenous administration of Tempol at the time of reperfusion reduced 2,3-DHBA production (Vehicle group: 472.2+/-196.2, Tempol group: 238.3+/-77.2) and the cerebral TBARS level (Vehicle group: 541.7+/-84.7, Tempol group: 339.0+/-147.2 nmol/g), and decreased the size of the cerebral infarction (Vehicle group: 202.2+/-98.4, Tempol group: 98.5+/-13.7 mm(3)). In contrast, Tempol administered 15 min prior to reperfusion reduced neither the TBARS level nor the size of the infarction. These results indicate that Tempol administration at the time of reperfusion reduced lipid peroxidation by scavenging free radicals, resulting in a reduction of the infarct size.
authors.affiliation: Department of Neurosurgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, 305-8575, Ibaraki, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kato
authors.forename: Kiyoyuki
authors.initials: K
authors.lastname: Yanaka
authors.forename: Koji
authors.initials: K
authors.lastname: Hyodo
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Homma
authors.forename: Sohji
authors.initials: S
authors.lastname: Nagase
authors.forename: Tadao
authors.initials: T
authors.lastname: Nose
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D062385:Hydroxybenzoates / Q000032:analysis; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D017551:Microdialysis; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000473:pathology; D013113:Spin Labels; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D013997:Time Factors
chemical_list: D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D062385:Hydroxybenzoates; D013113:Spin Labels; D017392:Thiobarbituric Acid Reactive Substances; C009135:2,3-dihydroxybenzoic acid; C001803:tempol