Effect of Acute Treatment with Dimethylnitrosamine on the Contents of Cytochromes and on the Activities of δ-Aminolevulinic Acid Synthetase, Heme Oxygenase and Drug-Metabolizing Enzymes in the Liver of Rats

Abstract

The effects of acute treatment with dimethylnitrosamine (DMN) on the contents of cytochromes and on the activities of key enzymes in heme metabolic pathways were investigated in male Wistar rats.Oral administration of DMN at a single dose of 30mg/kg markedly decreased the contents of microsomal cytochrome P-450 and b5, and this depression remained during 7 days after treatment. On the other hand, the activity of heme oxygenase was enhanced by 140% at 1 day, reached a peak (about 335% of the control) at 2 days, and returned to the initial level at 7 days after treatment. However, no significant change was observed in the activity of δ-aminolevulinic acid synthetase throughout these experiments.The activities of aminopyrine demethylase, aniline hydroxylase, bilirubin UDP-glucuronyltransferase, NADPH-cytochrome c reductase and NADH-cytochrome b5 reductase were all markedly reduced at 2 or 3 days after DMN treatment. In contrast, the activities of serum GPT and GOT and the content of serum bilirubin were significantly increased at 2 or 3 days after treatment.In the case of phenobarbital pretreatment (80mg/kg/day for 3 days), no remarkable differences were seen in the activities of bilirubin UDP-glucuronyltransferase and of key enzymes in the heme metabolic pathways between groups given simultaneous treatment with phenobarbital and DMN and DMN treatment alone, although phenobarbital apparently potentiated the activities of serum GPT and GOT induced by DMN treatment.