Oxypurinol attenuates hydroxyl radical production during ischemia/reperfusion injury of the rat cerebral cortex: an ESR study.
Free radical generation and release from the cerebral hemispheres of rats subjected to four vessel occlusion followed by reperfusion was monitored using a cortical cup technique in conjunction with the spin-trapping agent alpha(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN). Electron spin resonance (ESR) was used to detect the presence of free radical adducts of POBN in the cortical superfusates. 30 min of ischemia plus reperfusion resulted in the release of .OH radical adducts during the period of ischemia and, especially, during the initial phases of reperfusion. No radical adducts were detectable 90 min after the onset of reperfusion. Pretreatment with the xanthine oxidase inhibitor, oxypurinol (40 mg/kg i.p.), virtually abolished free radical formation and release. The results of this study are consistent with earlier evidence of free radical formation during ischemia/reperfusion and suggest that the cerebroprotective actions of oxypurinol may be related to its ability to prevent the cascade of free radical generation.
Phillis
J W
JW
Department of Physiology, Wayne State University, Detroit, MI 48201.
Sen
S
S
D000818:Animals; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D017665:Hydroxyl Radical; D008297:Male; D009589:Nitrogen Oxides; D010117:Oxypurinol / Q000494:pharmacology*; D011725:Pyridines; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism*; D013113:Spin Labels
D009589:Nitrogen Oxides; D011725:Pyridines; D013113:Spin Labels; C043438:alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone; D017665:Hydroxyl Radical; D010117:Oxypurinol