COMPARISON OF THERMALLY OXIDIZED LIPIDS AND ACETAMINOPHEN WITH CONCURRENT CONSUMPTION OF ETHANOL AS INDUCERS OF LIVER-CIRRHOSIS

The mechanism(s) of liver damage initiated by ingestion of toxic compo nents of thermally oxidized lipids was compared in a rat model with th e documented mechanisms of hepatic failure and necrosis initiated by a cetaminophen. Acetaminophen (50 mg/kg body weight) or oxidized lipids (0.15 ml oxidized trilinolein or 1.05 ml oxidized butter oil per rat) were intubated at 12-h intervals to rats. Treated rats were allowed fr ee access to food and water containing 3% ethanol. Changes in relative concentration of acute-phase plasma proteins, determined by two-dimen sional (2D) immunoelectrophoresis, were taken as a marker of liver dam age. In contrast to simple inflammation, acute-phase plasma proteins i n this study disproportionately increased or decreased as histological damage of the liver due to intubation oxidized lipids or acetaminophe n. Histological examination of liver of rats intoxicated with oxidized lipids revealed severe liver cirrhosis at the end of the trial, where the remaining viable hepatocytes were separated in a matrix of collag en. [H-3(1)]Thymidine incorporation in hepatic DNA of acetaminophen or oxidized lipid intoxication increased in the early stages of intoxica tion, indicative of regenerative activity of the liver. Further progre ssion of the cirrhosis inhibited continued liver regeneration and [H-3 (1)]thymidine incorporation into hepatic DNA. The cirrhotic liver at t his stage failed to regenerate to the original mass upon 75% partial h epatectomy. Therefore, it may be concluded that hepatic necrosis produ ced by oxidized lipids or by acetaminophen may have similar mechanisms .