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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.
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M Sommer, and
M Kretzschmar, and
T Zimmermann, and
V U Buko, and
O Lukivskaya, and
R Dargel
April 2002,
Journal of hepatology,
D Müller, and
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T Zimmermann, and
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R Dargel
January 2010,
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January 1998,
European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes,
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Liver international : official journal of the International Association for the Study of the Liver,
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January 1980,
Histochemistry,
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January 1986,
Experimental pathology,
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July 1994,
Toxicology and applied pharmacology,
D Müller, and
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R Dargel
August 1996,
The Journal of steroid biochemistry and molecular biology,
D Müller, and
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R Dargel
March 1991,
Bulletin of environmental contamination and toxicology,
D Müller, and
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T Zimmermann, and
V U Buko, and
O Lukivskaya, and
R Dargel
January 1991,
Histology and histopathology,
