Influence of Carbon Tetrachloride on Inducible Liver Enzymes and Response to Endotoxin in Mice

Abstract

Injection of mice with a sublethal dose of endotoxin 2 hr. after administration of 0.1 ml of carbon tetrachloride (CCl4) killed 75% of the animals. CCl4 alone killed no controls. Significant protection against this effect was afforded by 5 mg of cortisone and by 5 mg of nicotinamide adenine dinucleotide (NAD). With a larger dose of endotoxin, cortisone did not give protection. Liver tryptophan pyrrolase activity was lowered 2 hr. after CCl4 injection and reached a minimum after 17 hr. Induction of tryptophan pyrrolase by cortisone, followed by administration of CCl4, resulted in rapid loss of activity. A significant induction of tyrosine-[alpha]-ketoglutarate transaminase was observed in CCl4-treated mice. The induction of this enzyme by cortisone was somewhat impaired when CCl4 was administered concurrently with the hormone. CCl4 did not lower tryptophan pyrrolase in endotoxin-tolerant mice after 4 hr., but at 17 hr., the activity was decreased as much as in control mice. Oxidized pyridine nucleotides were decreased 17 hr. after administration of CCl4. This loss was prevented by administration of NAD (5 mg) or by cortisone (5 mg). Carbon clearance from blood was reduced after treatment with CCl4. These results indicate a degree of similarity between the metabolic effects of endotoxin and CCl4 in that both depress tryptophan pyrrolase and prevent its induction by cortisone, and both induce tyrosine transaminase in intact mice. Both substances appear to exert these effects through some type of mediated reaction.