Lipid peroxidation in thioacetamide-induced macronodular rat liver cirrhosis
| Autor: | Rolf Dargel, Oxana J. Lukivskaya, D. Müller, Thomas Zimmermann, Vyacheslav Buko, Manfred Sommer, M. Kretzschmar |
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| Rok vydání: | 1991 |
| Předmět: |
medicine.medical_specialty
Health Toxicology and Mutagenesis Phospholipid Thioacetamide Toxicology Liver Cirrhosis Experimental Lipid peroxidation chemistry.chemical_compound Cytochrome P-450 Enzyme System Internal medicine medicine Animals Epoxide hydrolase Phospholipids Fatty Acids Rats Inbred Strains General Medicine Glutathione Malondialdehyde Rats medicine.anatomical_structure Endocrinology chemistry Liver Hepatocyte Microsome Female Lipid Peroxidation |
| Zdroj: | Archives of toxicology. 65(3) |
| ISSN: | 0340-5761 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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