The release of proinflammatory cytokines by endotoxins and during oxidative stress is considered to be an early key step in the pathogenesis of alcoholic liver disease (ALD). Ethanol-inducible cytochrome P450 2E1 (CYP2E1) has potentially pro-oxidative and toxicological properties, and its expression
Combined effect of ethanol and carbon disulphide on cytochrome P-450 monooxygenase, lipid peroxidation and ultrastructure of the liver in chronically exposed rats
✍ Scribed by Teresa Wrońska-Nofer; Jadwiga Klimczak; Justyna M. Wiśniewska-Knypl; Jolanta Jajte; Barbara Opalska
- Publisher
- John Wiley and Sons
- Year
- 1986
- Tongue
- English
- Weight
- 747 KB
- Volume
- 6
- Category
- Article
- ISSN
- 0260-437X
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✦ Synopsis
A 5-month treatment of rats with ethanol (10% solution in drinking water) stimulated aniline p-hydroxylase and the microsomal ethanol oxidizing system (MEOS) by 140 and 70%, respectively, cytochrome P-450 by 22% and accompanied by lipid peroxidation by 40% in microsomes. It also caused smooth endoplasmic reticulum (SER) proliferation and rough endoplasmic reticulum (RER) degranulation in hepatocytes.
Repeated inhalatory exposure of rats to 1.5 g/m3 of CS,, 5 h daily, 5 days a week for 5 months decreased aniline p-hydroxylase and MEOS by 70 and 55% respectively, doubled hexobarbital sleeping time and depressed cytochrome P-450 by 30% and its conversion to cytochrome P-420; these effects were accompanied by the appearance of cytochrome P-420, the intensification of lipid peroxidation in microsomes and some degranulation of RER in hepatocytes. Combined exposure of rats to ethanol and CS, resulted in a significant potentiation of the inhibitory effects of CS, on cytochrome P-450 mono-oxygenase and MEOS but with enhancement of CS, effects on the liver microsomal mono-oxygenase, but CS, decreased the effect of ethanol on SER proliferation. The interaction both on the biochemical and the morphological level can be explained with the ethanol-stimulated biotransformation of CS, to reactive electrophilic derivative(s), the subsequent destruction of cytochrome P-450 to cytochrome P-420 and the intensification of lipid peroxidation.
forced to drink 10% ethanol as sole source of fluid.'O Experiments reported here revealed that ethanol did, in fact, potentiate the depressive effect of CS, on cytochrome P-450 mono-oxygenase.
to CS, in the majority of countries is 30 mg/m P )' and
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