Amflutizole, a xanthine oxidase inhibitor, inhibits free radical generation in the ischemic/reperfused rat cerebral cortex.
Free radical generation and release from the cerebral hemispheres of rats subjected to four-vessel occlusion elicited cerebral ischemia/reperfusion was monitored using a cortical cup technique 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. Thirty min of ischemia plus reperfusion resulted in the release of .OH radical adducts during ischemia and especially in the initial stages of reperfusion. Pretreatment with the xanthine oxidase inhibitor, amflutizole (30 mg/kg) virtually abolished free radical formation and release. These results are consistent with earlier evidence that xanthine oxidase activity contributes to free radical formation in the ischemic/reperfused rat brain.
Phillis
J W
JW
Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201.
Sen
S
S
Cao
X
X
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002545:Brain Ischemia / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004569:Electroencephalography; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000378:metabolism; D008297:Male; D009589:Nitrogen Oxides; D011725:Pyridines; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D013113:Spin Labels; D013844:Thiazoles / Q000494:pharmacology*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
D005609:Free Radicals; D009589:Nitrogen Oxides; D011725:Pyridines; D013113:Spin Labels; D013844:Thiazoles; C043438:alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone; C046749:amflutizole; D014969:Xanthine Oxidase