title: Role of xanthine oxidase in ischemia/reperfusion injury.
abstract: Oxygen metabolites formed during reperfusion of ischemic kidneys prevent recovery of renal function after short periods of renal ischemia. Xanthine oxidase has been proposed as a source of toxic oxygen metabolites during reperfusion of ischemic kidneys. To determine whether the enzyme is converted from the non-oxygen metabolite-producing dehydrogenase (type D) to the oxygen metabolite-producing oxidase (type O), we measured type D and type O (total, reversible, and irreversible) xanthine oxidase in renal cortical homogenates after 30 min of ischemia in vivo and 60 min of reperfusion by the isolated perfused kidney technique. Total enzyme activity (type D plus type O) was not altered by ischemia or reperfusion. Compared with nonischemic conditions, ischemia increased total type O (53 +/- 5 vs. 21 +/- 3%, P less than 0.01) and reversible type O (15.4 +/- 1.5 vs. 2.1 +/- 1.4 U/g) xanthine oxidase activities. Reperfusion further increased total type O (82 +/- 3%) and reversible type O (27.7 +/- 3.3 U/g, both P less than 0.01 vs. nonischemic perfusions) xanthine oxidase activities. To determine the physiological role of xanthine oxidase in renal ischemia, we depleted rats of xanthine oxidase by feeding tungsten. After 4 wk of tungsten, renal xanthine oxidase levels were reduced by greater than 90% and renal function was markedly improved during reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: University of Colorado School of Medicine, Webb-Waring Lung Institute, Denver General Hospital 80204-4507.
authors.forename: S L
authors.initials: SL
authors.lastname: Linas
authors.forename: D
authors.initials: D
authors.lastname: Whittenburg
authors.forename: J E
authors.initials: JE
authors.lastname: Repine
mesh_terms: D000818:Animals; D007668:Kidney / Q000503:physiopathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation; D014414:Tungsten / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*
chemical_list: D014969:Xanthine Oxidase; D014414:Tungsten