Combined effect of ethanol and carbon disulphide on cytochrome P‐450 monooxygenase, lipid peroxidation and ultrastructure of the liver in chronically exposed rats

Abstract

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 CS2, 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 CS2 resulted in a significant potentiation of the inhibitory effects of CS2 on cytochrome P-450 mono-oxygenase and MEOS but with enhancement of CS2 effects on the liver microsomal mono-oxygenase, but CS2 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 CS2 to reactive electrophilic derivative(s), the subsequent destruction of cytochrome P-450 to cytochrome P-420 and the intensification of lipid peroxidation.

Toxic effects of combined treatment of 1,2‐dichloroethane and ethanol on mouse brain and the related mechanisms

“…Recent studies have shown that combined exposure to ethanol and halogenated hydrocarbon compounds induces liver toxicity. At present, studies on the hepatotoxicity of combined exposure to ethanol and carbon tetrachloride are the most comprehensive . CCl 4 is commonly accepted as a typical toxicant, and CCl 4 ‐induced liver injury was a classic model of chemical liver toxicity .…”

Potentiation of the hepatic toxicity of carbon disulfide by chlordane

“…[10] Studies reported by Wronska-Nofer et al ., indicate that simultaneous exposure to ethanol over a long period results in potentiation of CS 2 hepatotoxicity, probably as a result of CYP2E1 induction by ethanol. [11] Even though these studies implicate CYP2E1 and PB-inducible CYPs in the metabolism and toxicity of CS 2 , it is not known whether many other CYP inducers may have a potentiating effect on the hepatotoxicity of CS 2 . Studies in our laboratory and those by others have shown that even at very low levels, chlordane (CLD) is a powerful inducer of various CYPs, especially CYP2B1 which is also induced by PB.…”