Effect of allopurinol on oxidant stress and hepatic function following ischemia and reperfusion in the rat.
Reactive oxygen species generated by xanthine oxidase during reperfusion of ischemic liver might in part be responsible for ischemic organ injury. Therefore, the effect of allopurinol, an inhibitor of xanthine oxidase, on the oxidant stress associated with reperfusion and on hepatic function 24 h after ischemia was assessed in a model of partial hepatic ischemia in rats. The increase in circulating glutathione disulfide (GSSG) was used as an index of oxidant stress. Hepatic function was assessed using a breath test to quantitative the demethylation of aminopyrine in vivo. In control animals the plasma concentration of GSSG 1 h after onset of reperfusion increased from 0.9 mumol/l in sham-operated controls to 4.2, 5.5, and 8.0 mumol/l following 45, 90 and 120 min of ischemia, respectively. The percent of the administered dose of (dimethylamine-14C)-aminopyrine appearing in breath as 14CO2 was not significantly different from sham-operated controls (40.2%) 24 h after 45 min of ischemia (34.1%), but decreased progressively to 26.0% (p less than 0.05) and 20.6% (p less than 0.05) after 90 and 120 min of ischemia, respectively. Allopurinol, administered at a dose of 50 mg/kg 18 h and 1 h prior to ischemia, did not prevent the rise in plasma GSSG, did not alleviate the release of transaminases, and did not improve the demethylation of aminopyrine 24 h after ischemia, suggesting that reactive oxygen species generated by xanthine oxidase during reperfusion of ischemic liver do not contribute significantly to ischemic injury.
Metzger
J
J
Department of Clinical Pharmacology, University of Berne, Switzerland.
Lauterburg
B H
BH
D000493:Allopurinol / Q000627:therapeutic use*; D000818:Animals; D005609:Free Radicals; D005978:Glutathione / Q000031:analogs & derivatives / Q000097:blood; D019803:Glutathione Disulfide; D008099:Liver / Q000098:blood supply*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000188:drug therapy*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D005609:Free Radicals; D000493:Allopurinol; D014969:Xanthine Oxidase; D005978:Glutathione; D019803:Glutathione Disulfide