Changes in liver nucleotide concentrations in experimental liver injury. 1. Carbon tetrachloride poisoning

Abstract

The concentrations of nicotinamide adenine dinucleotide (NAD), reduced nicotinamide adenine dinucleotide (NADH2) nicotinamide adenine dinucleotide phosphate (NADP) and reduced nicotinamide adenine dinucleotide phosphate (NADPH2) in rat liver were determined at various times after enteral dosing with a CCl4 tetrachloride-liquidparaffin mixture (dose of CCl4, 0-125 m./100 g body weight). Compared with control groups receiving liquid paraffin alone, the administration of CCl4 had little significant effect on the concentrations and relative proportions of NAD and NADH2 during the period studied (0-18 hours). In contrast, the administration of CCl4 resulted in rapid changes in the NADP and NADPH2 concentrations. There were falls in NADPH2 and rises in NADP contents respectively. These changes resulted in considerable variations in the NADPH2: NADP ratio. Administration of the antihista-mine drug Phenergan prevented these changes in NADP and NADPH2 concentrations resulting from the administration of CCl4. The probable implications of the changes in NADPH2 and NADP concentrations to the mechanisms of necrosis are discussed. During the first 30 minutes after the ingestion of CCl4 the changes that are found in the NADP and NADPH2 concentrations are related in a direct manner to the necrogenic chain of reactions.