Imai Hideaki, Graham David Ian, Masayasu Hiroyuki, Macrae Iseabail Mhairi
Wellcome Surgical Institute and Department of Neuropathology, University of Glasgow, Glasgow, UK.
Free Radic Biol Med. 2003 Jan 1;34(1):56-63. doi: 10.1016/s0891-5849(02)01180-2.
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).
已在实验性中风中研究了谷胱甘肽过氧化物酶模拟物依布硒啉的抗氧化和神经保护潜力。在大鼠永久性大脑中动脉闭塞前45分钟开始静脉输注依布硒啉（1毫克/千克/小时）或赋形剂，并持续至实验结束。使用针对识别2'-脱氧鸟苷羟基化产物（8-羟基脱氧鸟苷/8-氧代脱氧鸟苷）的DNA损伤抗体和针对识别4-羟基壬烯醛组氨酸加合物（4-HNE）的脂质过氧化抗体，通过免疫组织化学评估大脑氧化损伤的地形和范围。用标准组织病理学绘制并评估缺血性损伤。在接受赋形剂治疗的大鼠中，8-氧代脱氧鸟苷和4-HNE的免疫阳性染色超出了缺血性损伤的边界。在接受依布硒啉治疗的大鼠中，8-氧代脱氧鸟苷和4-HNE的组织免疫阳性范围小于显示缺血性损伤的范围，证实了其在体内的抗氧化作用机制。此外，依布硒啉治疗使皮质缺血性损伤减少了28%（p<.02）。
