title: Antioxidant ebselen reduces oxidative damage in focal cerebral ischemia.
abstract: The antioxidant and neuroprotective potential of the glutathione peroxidase mimic ebselen has been investigated in experimental stroke. Intravenous ebselen (1 mg/kg/h) or vehicle infusion was started 45 min before permanent middle cerebral artery occlusion in the rat, and continued until the end of the experiment. The topography and extent of oxidative damage to the brain was assessed immunohistochemically using an antibody for DNA damage that identified hydroxylated products of 2'-deoxyguanosine (8-OHdG/8-oxodGuo) and an antibody for lipid peroxidation that identified the 4-hydroxynonenal histidine adduct (4-HNE). Ischemic damage was mapped and evaluated with standard histopathology. In the vehicle-treated rats immunopositive staining for both 8-oxodGuo and 4-HNE extended beyond the boundary of ischemic damage. In ebselen-treated rats, the extent of tissue immunopositive for 8-oxodGuo, and 4-HNE was less than that demonstrating ischemic damage confirming the antioxidant mechanism of action in vivo. In addition, ebselen treatment induced a 28% reduction in cortical ischemic damage (p <.02).
authors.affiliation: Wellcome Surgical Institute and Department of Neuropathology, University of Glasgow, Glasgow, UK.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Imai
authors.forename: David Ian
authors.initials: DI
authors.lastname: Graham
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Masayasu
authors.forename: Iseabail Mhairi
authors.initials: IM
authors.lastname: Macrae
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D001393:Azoles / Q000097:blood / Q000494:pharmacology*; D002545:Brain Ischemia / Q000378:metabolism / Q000517:prevention & control*; D007150:Immunohistochemistry; D054833:Isoindoles; D008297:Male; D016566:Organoselenium Compounds / Q000097:blood / Q000494:pharmacology*; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000975:Antioxidants; D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; C042986:ebselen