ROLE OF KUPFFER-CELLS IN REPERFUSION INJURY IN FAT-LOADED LIVERS FROMETHANOL-TREATED RATS

Reperfusion injury was studied in blood-free perfused livers from fat- loaded, ethanol-treated rats. Rats were pair-fed a modified Lieber-DeC arli liquid diet containing 36% calories as ethanol or isocaloric malt ose-dextrin for 4 to 5 weeks. Reperfusion injury to the liver, which o ccurs in previously hypoxic regions upon reintroduction of oxygen, was studied in a low-flow, reflow perfusion model. Lactate dehydrogenase in effluent perfusate increased from basal levels of < 1 to 17 IU/g/h in livers from controls, whereas prior alcohol treatment elevated valu es to 37 IU/g/h. Pretreatment of rats with gadolinium chloride (GdCl3, 20 mg/kg i.v.), a selective Kupffer cell toxicant, minimized lactate dehydrogenase release during reperfusion to 7 to 8 IU/g/h in livers fr om both groups. Rates of malondialdehyde production were 144 and 166 n mol/g/h during reperfusion in control and alcohol-treated rats, respec tively, but values reached only 54 and 79 nmol/g/h after GdCl3 treatme nt. Interestingly, a typical PBN/carbon-centered free radical adduct s ignal was detected in bile of livers from ethanol-treated rats, but no t in controls or ethanol-treated rats given GdCl3. Portal pressure inc reased during the reperfusion period in livers from alcohol-treated ra ts, although not in controls, and GdCl3 reduced it significantly. Take n together, these data indicate that reperfusion injury is greater in fatty livers from alcohol-treated rats in a blood-free model. Inactiva tion of Kupffer cells minimized reperfusion injury in both control and alcohol-treated rats, most likely by diminishing lipid peroxidation t hereby improving hepatic microcirculation.