1. Hypovolaemic shock associated with surgical trauma has been studied in a rat liver ischaemia-reperfusion model by determination of oxidative stress, lipid peroxidation and tissue infiltration of polymorphonuclear leucocytes. 2. Liver ischaemia alone resulted in slight liver oedema and polymorphonuclear leucocyte infiltration, a slight increase in thiobarbituric acid-reacting substances (an index of lipid peroxidation) and decreases in liver reduced glutathione and total radical-trapping antioxidant parameter, indices of oxidative stress. Ischaemia plus 30 min of reperfusion further increased liver oedema, polymorphonuclear leucocyte infiltration and thiobarbituric-acid reacting substances, and further decreased liver reduced glutathione and total radical-trapping antioxidant parameter. 3. After 60 and 90 min of reperfusion, oedema (40% increase), polymorphonuclear leucocyte infiltration (40-fold increase) and thiobarbituric-acid reacting substances (20-fold increase) were maximal, and liver reduced glutathione (75–95% decrease) and total radical-trapping antioxidant parameter (85–90% decrease) were at a minimum. 4. All parameters were exacerbated by 24 h starvation. Liver reduced glutathione closely paralleled total radical-trapping antioxidant parameter, and ischaemia alone depleted both by 30% in fed rats and 50% in fasted rats. 5. Oxidative stress and lipid peroxidation were associated more with the period of reperfusion and polymorphonuclear leucocyte infiltration. Polymorphonuclear leucocyte infiltration into lung also occurred after 90 min of liver reperfusion. 6. Possible mechanisms of hepatic ischaemia-reperfusion-induced oxidative stress are discussed.
1. After oral administration of [ 14 C]carbenoxolone (100 mg, 5 μCi) to patients with radiologically-proven gastric ulcers the radioactivity was excreted mostly in the faeces (70–80%) with lesser amounts in the expired CO 2 (12–20%) and only traces in the urine (0·2–1%). This is in marked contrast with the metabolism and pattern of excretion of this drug in the rat. 2. Most of the radioactivity excreted in the faeces of patients was present as carbenoxolone, which was probably formed by bacterial hydrolysis of the biliary-excreted conjugate of carbenoxolone. 3. It is concluded that in man orally administered carbenoxolone is absorbed mostly unchanged, in contrast with the rat in which the orally administered drug is substantially hydrolysed to β-glycyrrhetic acid and succinic acid before absorption.