Ethanol, not fat accumulation per se, increases free radical production ina low-flow, reflow liver perfusion model

Background Ethanol increases primary graft failure after liver transplantat ion, yet whether it acts via mechanisms involving fat accumulation remains unclear. Methods. Rats were pair-fed a modified Lieber-De-Carli liquid diet containi ng 35% (high-fat) or 12% (low-fat) of calories as fat combined with 36% of calories as ethanol or isocaloric maltose-dextrin for 4-5 weeks. Reperfusio n injury to the liver was studied using a low-flow, reflow perfusion model and a liver transplantation model, and free radicals were detected using el ectron spin resonance and the spin trapping technique. Results. As expected, basal hepatic triglycerides were similar in livers fr om rats fed low- and high-fat control diets. Ethanol did not alter triglyce ride levels significantly in rats fed a low-fat diet, but increased values about 2.4-fold in rats fed a high-fat diet. Ethanol increased lactate dehyd rogenase release during reperfusion from 10 to 26 IU/g/h in rats fed a low- fat diet and from 17 to 34 IU/g/h in rats fed a high-fat diet, respectively . Portal pressure increased from about 3 to 10.5 cm H2O upon reperfusion in livers from high-fat, ethanol-fed rats, but only reached values of 9.1 in the low-fat, ethanol-fed group. A free radical adduct signal was detected i n the bile of livers from ethanol-treated rats, and the magnitude of this s ignal was similar in livers of ethanol-treated rats fed high- or low-fat di ets. However, radical adducts could not be detected in either group in the absence of dietary ethanol, Moreover, 67-77% rats given low-fat or high-fat control diets survived after liver transplantation, but only 11% survived if treated with ethanol, Conclusions. It is concluded that ethanol plays a major role in hepatic rep erfusion injury, most likely via mechanisms involving free radicals. Increa sed hepatic fat content alone plays only a minor role, probably by causing slight disturbances in the hepatic microcirculation.