Allopurinol improves scavenging ability of the liver after ischemia/reperfusion injury.
Deterioration of energy metabolism and oxidative stress represent fundamental mechanisms in ischemia and reperfusion injury. In a normothermic 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 liver lobes followed by 24 h observation. The overall liver function was 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 hepatocyte function as bile flow improved significantly in this group after 1 and 24 h of reperfusion compared with that of controls. Oxidative stress was also significantly attenuated in this group, as efflux of glutathione 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 controls. All given in a concentration 50 mg/kg had some, but a non-significant, effect. We conclude that biliary glutathione is an important marker of oxidative stress and may reflect the scavenging ability of the liver after ischemic injury. Significant correlation of bile flow with biliary glutathione during reperfusion indicates that oxidative stress is an important mechanism attenuating liver function after ischemia/reperfusion injury.
Karwinski
W
W
Department of Surgery, Deaconess Hospital, University of Bergen, Norway.
Søreide
O
O
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D001646:Bile / Q000737:chemistry / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005978:Glutathione / Q000032:analysis; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*; D014968:Xanthine Dehydrogenase / Q000037:antagonists & inhibitors; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D000493:Allopurinol; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase; D005978:Glutathione