Effects of acute CS 2 intoxication on liver protein and drug metabolism

Abstract

Rats pretreated with phenobarbitone and their controls were exposed to 0.15% atmospheric CS 2 for 2 h. Liver protein metabolism and microsomal drug metabolizing enzyme activities were analyzed 1, 4 and 46 h later. In the pretreated rats the [ 14C]leucine uptake was at first inhibited, then liver RNA tended to increase. This increase was followed by a decline in the [ 14C]leucine uptake, while RNA content diminished to the control level. In the control rats (not pretreated with phenobarbital) the effects of CS 2 on liver protein metabolism were less; only at 4 h after the exposure was liver RNA increased and [ 14C]leucine uptake slightly stimulated. In the pretreated rats CS 2 had decreased microsomal P-450 by about 50% at 1 and 4 h, and the activity of 7-O-dealkylase of ethoxycoumarin had decreased even more. The measurable UDPglucuronosyltransferase of the liver microsomes of the pretreated rats had increased by 26% at 1 h and by 80% at 4 h after the CS 2 exposure. The in vivo activation of microsomal UDPglucuronosyltransferase may result from a stimulated lipid peroxidation of reticuloendothelial membranes by CS 2 metabolites in vivo, as suggested by the diene conjugation spectra. In control rats CS 2 depressed only the ethoxycoumarin deethylase activity. All the microsomal changes caused by CS 2 exposure were restored within 46 h. It is suggested that the different action of CS 2 on the liver protein metabolism of rats pretreated with phenobarbitone and controls results from the different stage of protein turnover in the two groups, i.e. in the barbituratetreated animals there is a phase of increased protein synthesis and accordingly the protein turnover is more sensitive to the action of CS 2.