DELETERIOUS EFFECTS OF XANTHINE-OXIDASE ON RAT-LIVER ENDOTHELIAL-CELLS AFTER ISCHEMIA-REPERFUSION

Previous studies have demonstrated that reactive oxygen species are in volved in ischemic injury. The present work was undertaken to determin e in vivo the role of xanthine oxidase in the oxygen free radical prod uction during rat liver ischemia and to examine the activity of antiox idant enzymes (superoxide dismutase, catalase and glutathione peroxida se) during the same period. Our results indicate a 4-fold increase in xanthine oxidase activity between 2 and 3 hours of normothermic ischem ia, in parallel with a decrease in cell viability. Moderate hypothermi a delays both events. Under the same conditions, the activity of oxyge n radical scavenging enzymes remains unchanged. Moreover, we have comp ared in vitro the susceptibility of isolated liver cells to an oxidati ve stress induced by O-2(-), H2O2 and (OH)-O-.. Our results reveal tha t endothelial cells are much more susceptible to reactive oxygen speci es than hepatocytes, probably because they lack H2O2-detoxifying enzym es. These findings suggest that xanthine oxidase might play a major ro le in the ischemic injury mainly at the level of the sinusoidal space where most endothelial cells are located.