Role of xanthine oxidase in ischemia/reperfusion injury

SL Linas, D Whittenburg… - American Journal of …, 1990 - journals.physiology.org
SL Linas, D Whittenburg, JE Repine
American Journal of Physiology-Renal Physiology, 1990journals.physiology.org
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 …
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)
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