Xanthine oxidase-derived hydrogen peroxide contributes to ischemia reperfusion-induced edema in gerbil brains.
The contribution of toxic O2 metabolites to cerebral ischemia reperfusion injury has not been determined. We found that gerbils subjected to temporary unilateral carotid artery occlusion (ischemia) consistently developed neurologic deficits during ischemia with severities that correlated with increasing degrees of brain edema and brain H2O2 levels after reperfusion. In contrast, gerbils treated just before reperfusion (after ischemia) with dimethylthiourea (DMTU), but not urea, had decreased brain edema and brain H2O2 levels. In addition, gerbils fed a tungsten-rich diet for 4, 5, or 6 wk developed progressive decreases in brain xanthine oxidase (XO) and brain XO + xanthine dehydrogenase (XD) activities, brain edema, and brain H2O2 levels after temporary unilateral carotid artery occlusion and reperfusion. In contrast to tungsten-treated gerbils, allopurinol-treated gerbils did not have statistically significant decreases in brain XO or XO + XD levels, and reduced brain edema and brain H2O2 levels occurred only in gerbils developing mild but not severe neurologic deficits during ischemia. Finally, gerbils treated with DMTU or tungsten all survived, while greater than 60% of gerbils treated with urea, allopurinol, or saline died by 48 h after temporary unilateral carotid artery occlusion and reperfusion. Our findings indicate that H2O2 from XO contributes to reperfusion-induced edema in brains subjected to temporary ischemia.
D000493:Allopurinol / Q000627:therapeutic use; D000818:Animals; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry; D001929:Brain Edema / Q000209:etiology* / Q000517:prevention & control; D002545:Brain Ischemia / Q000150:complications*; D005260:Female; D005849:Gerbillinae; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008297:Male; D009422:Nervous System Diseases / Q000517:prevention & control; D013890:Thiourea / Q000031:analogs & derivatives / Q000627:therapeutic use; D014414:Tungsten / Q000627:therapeutic use; D014508:Urea / Q000627:therapeutic use; D014969:Xanthine Oxidase / Q000378:metabolism*
D000493:Allopurinol; C038983:1,3-dimethylthiourea; D014508:Urea; D006861:Hydrogen Peroxide; D014969:Xanthine Oxidase; D013890:Thiourea; D014414:Tungsten