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Lipid peroxidation in thioacetamide-induced macronodular rat liver cirrhosis
D Müller1, M Sommer, M Kretzschmar
1Institute of Pathological Biochemistry, Friedrich Schiller University, Jena, Soviet Union.
Abstract:
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.
Insights
Lipid peroxidation is altered in thioacetamide-induced liver cirrhosis. Microsomes showed decreased malondialdehyde production, while hepatocytes exhibited increased levels, indicating differential responses in cirrhotic rat livers.
Area of Science:
- Biochemistry
- Toxicology
- Cell Biology
Background:
- Thioacetamide (TAA) induces macronodular cirrhosis in rat livers.
- Lipid peroxidation is a key process in liver injury.
Purpose of the Study:
- To analyze lipid peroxidation in microsomes and hepatocytes from TAA-induced cirrhotic rat livers.
- To investigate the effects of TAA on cytochrome P450 content and enzyme activities.
- To assess the impact of TAA on hepatocellular glutathione levels and redox state.
Main Methods:
- Induction of liver cirrhosis using thioacetamide in rats.
- Measurement of malondialdehyde (MDA) formation as an indicator of lipid peroxidation.
- Analysis of cytochrome P450 content and enzyme activities (e.g., ethylmorphine N-demethylase).
- Assessment of phospholipid fatty acid composition.
- Quantification of glutathione (GSH) and glutathione disulfide (GSSG) levels.
Main Results:
- Microsomes from cirrhotic livers showed decreased MDA production when stimulated.
- Hepatic microsomes exhibited reduced cytochrome P450 content and enzyme activities.
- Phosphatidylcholine and phosphatidylethanolamine fatty acid patterns were altered in microsomes.
- Isolated hepatocytes from cirrhotic livers displayed increased MDA formation.
- Hepatocellular GSH levels were unaffected, but GSSG increased, reducing the GSH/GSSG ratio.
- Verapamil demonstrated antioxidative properties by inhibiting lipid peroxidation in hepatocytes.
Conclusions:
- Lipid peroxidation is significantly altered in thioacetamide-induced liver cirrhosis.
- Microsomes and hepatocytes from cirrhotic livers exhibit differential responses to prooxidant stimuli.
- TAA-induced cirrhosis affects microsomal enzyme activities and fatty acid composition.