ALLOPURINOL IMPROVES SCAVENGING ABILITY OF THE LIVER AFTER ISCHEMIA REPERFUSION INJURY/

Deterioration of energy metabolism and oxidative stress represent fund amental mechanisms in ischemia and reperfusion injury. In a normotherm ic ischemia/reperfusion rat model, we investigated whether allopurinol (ALL) may improve the scavenging ability of the liver after ischemia. ALL was given prior to ischemia and reperfusion (concentration 100 or 50 mg/kg) and controls were given a placebo. After a basal period of 30 min, 1 h normothermic ischemia was induced in the median and left l iver lobes followed by 24 h observation. The overall liver function wa s assessed by bile secretion, and free oxygen production was assessed by glutathione efflux into bile during the first 60 min of reperfusion and at 24 h. Allopurinol (concentration 100 mg/kg) protected hepatocy te function as bile flow improved significantly in this group after 1 and 24 h of reperfusion compared with that of controls. Oxidative stre ss was also significantly attenuated in this group, as efflux of gluta thione into bile was significantly higher in the ALL group (100 mg/kg) after 24 h but not after 1 h of reperfusion compared with that of con trols. ALL given in a concentration 50 mg/kg had some, but a non-signi ficant, effect. We conclude that biliary glutathione is an important m arker of oxidative stress and may reflect the scavenging ability of th e liver after ischemic injury. Significant correlation of bile flow wi th biliary glutathione during reperfusion indicates that oxidative str ess is an important mechanism attenuating liver function after ischemi a/reperfusion injury.