Lipid peroxidation in thioacetamide-induced macronodular rat liver cirrhosis

• Published in: Archives of toxicology Vol. 65; no. 3; pp. 199 - 203
• Main Authors: MUÊLLER, D, SOMMER, M, KRETZSCHMAR, M, ZIMMERMANN, T, BUKO, V. U, LUKIVSKAYA, O. J, DARGEL, R
• Format: Journal Article
• Language: English
• Published: Berlin Springer 1991
• Subjects: Animals; Biological and medical sciences; Cytochrome P-450 Enzyme System - analysis; Fatty Acids - metabolism; Female; Lipid Peroxidation; Liver - metabolism; Liver Cirrhosis, Experimental - chemically induced; Liver Cirrhosis, Experimental - metabolism; Medical sciences; Miscellaneous; Phospholipids - metabolism; Rats; Rats, Inbred Strains; Thioacetamide - toxicity; Toxicology; Rat; Toxicity; Cytochrome P450; Liver; Rodentia; Lipids; Microsome; Fatty acids; Cirrhosis; Vertebrata; Mammalia; Hepatocyte; Animal; Digestive diseases; Mechanism of action; Peroxidation
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/BF02307309

Microsomes and isolated hepatocytes from thioacetamide (TAA)-induced macronodularly cirrhotic rat livers were analysed for their susceptibility to unstimulated and stimulated lipid peroxidation measured as malondialdehyde (MDA) formation. In microsomes from TAA-induced macronodularly cirrhotic livers the MDA production stimulated either by ascorbate-iron or by ADP-iron in a NADPH-regenerating system was decreased. Hepatic microsomes from TAA-treated rats exhibited a reduced cytochrome P450 content and lowered activities of ethylmorphine N-demethylase, ethoxycoumarin O-deethylase and epoxide hydrolase. Besides this, the microsomal fatty acid pattern of phosphatidylcholine and phosphatidylethanolamine was significantly changed after 6 months of TAA administration. The 18:2/20:4 ratio of phospholipid fatty acids was markedly increased. In contrast to the microsomes, in isolated hepatocytes from macronodularly cirrhotic livers the iron- and ascorbate-iron-stimulated MDA formation was increased. The hepatocellular GSH content was unaffected by TAA pretreatment, whereas the GSSG content exhibited a significant increase, thus leading to a pronounced reduction of the GSH/GSSG ratio. The calcium channel blocker verapamil (200 microM), known to be able to scavenge OH' radicals produced by the Fenton reaction, revealed an inhibitory effect on ascorbate-iron- and ADP-iron-stimulated lipid peroxidation in hepatocytes from normal as well as TAA-treated livers which is attributed to its antioxidative properties. In summary, lipid peroxidation is altered in TAA-induced macronodularly cirrhotic rat livers. Furthermore, the data clearly show that isolated microsomes and parenchymal cells prepared from cirrhotic livers react differently to prooxidant stimuli.