Combined effect of ethanol and carbon disulphide on cytochrome P‐450 monooxygenase, lipid peroxidation and ultrastructure of the liver in chronically exposed rats
1986; Wiley; Volume: 6; Issue: 4 Linguagem: Inglês
10.1002/jat.2550060412
ISSN1099-1263
AutoresT Wrońska-Nofer, Jadwiga Klimczak, Justyna M. Wiśniewska-knypl, Jolanta Jajte, Barbara Opalska,
Tópico(s)Eicosanoids and Hypertension Pharmacology
ResumoAbstract 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/m 3 of CS 2 , 5h 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 2 resulted in a significant potentiation of the inhibitory effects of CS 2 on cytochrome P‐450 mono‐oxygenase and MEOS but with enhancement of CS 2 effects on the liver microsomal mono‐oxygenase, but CS 2 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 2 to reactive electrophilic derivative(s), the subsequent destruction of cytochrome P‐450 to cytochrome P‐420 and the intensification of lipid peroxidation.
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