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 components of thermally oxidized lipids was compared in a rat model with the documented mechanisms of hepatic failure and necrosis initiated by acetaminophen. 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 free access to food and water containing 3% ethanol. Changes in relative concentration of acute-phase plasma proteins, determined by two-dimensional (2D) immunoelectrophoresis, were taken as a marker of liver damage. In contrast to simple inflammation, acute-phase plasma proteins in this study disproportionately increased or decreased as histological damage of the liver due to intubation oxidized lipids or acetaminophen. 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 collagen. [3H1]Thymidine incorporation in hepatic DNA of acetaminophen or oxidized lipid intoxication increased in the early stages of intoxication, indicative of regenerative activity of the liver. Further progression of the cirrhosis inhibited continued liver regeneration and [3H1]thymidine incorporation into hepatic DNA. The cirrhotic liver at this stage failed to regenerate to the original mass upon 75% partial hepatectomy. Therefore, it may be concluded that hepatic necrosis produced by oxidized lipids or by acetaminophen may have similar mechanisms.
Fouad
F M
FM
Department of Biochemistry, Memorial University of Newfoundland, St. John's, Canada.
Shahidi
F
F
Mamer
O A
OA
D000082:Acetaminophen / Q000633:toxicity*; D000210:Acute-Phase Reaction / Q000139:chemically induced; D000704:Analysis of Variance; D000818:Animals; D016227:Benzoquinones / Q000633:toxicity; D004247:DNA / Q000096:biosynthesis; D004347:Drug Interactions; D000431:Ethanol / Q000633:toxicity*; D006498:Hepatectomy; D006358:Hot Temperature; D007097:Imines / Q000633:toxicity; D050356:Lipid Metabolism; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D009336:Necrosis / Q000139:chemically induced; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms
D016227:Benzoquinones; D007097:Imines; D000082:Acetaminophen; D000431:Ethanol; C004532:quinone; D004247:DNA; C028473:N-acetyl-4-benzoquinoneimine