Uptake, metabolism, and secretion of 3'-methyl-N,N-dimethyl-4-aminoazobenzene by isolated perfused rat liver

Uptake, metabolism, and biliary secretion of 39-methyl-N,N-dimethyl-4-aminoazobenzene (39-Me-DAB) were studied in isolated rat liver which was perfused with protein-free fluorocarbon medium. [14C]39-Me-DAB (5-10 nmol) was injected into the portal vein and allowed to recirculate. The recovery of radioactivity in bile was 7.5, 14, and 20% at 15, 30, and 45 min of injection, respectively. At 45 min, the liver contained an additional 17% of injected radioactivity. Azo dye metabolites in perfused liver differed from those in vivo; metabolites co-migrating with 39-CHO-DAB and 39-methyl-n,n-methyl aminoazobenzene (Me-MAB) (and the parent compound 39-Me-DAB) were present, while metabolites co-migrating with 39-Me-49-OH-AB and 39-CH2OH-MAB were increased and metabolites co-migrating with 39-CH2OH-DAB were decreased. In bile from perfused liver, metabolites co-migrating with 39-CHO-DAB and 39-Me-MAB were undetectable. When proteins from normal rat bile were injected into portal vein 15 min after the administration of 39-Me-DAB, the compounds co-migrating with 39-Me-MAB, 39-CHO-DAB, 39-Me-49-OH-AB, and 39-CH2OH-MAB decreased, and compounds co-migrating with 39-CH2OH-DAB increased in the liver; in bile, there was increase in 39-Me-MAB, 39-CHO-DAB, and 39-Me-49-OH-MAB, which there was a decrease in N-Ac-39-Me-49-OH-AB and 39-COOH-DAB. Appearance of protein-metabolite adducts in bile was also observed after addition of normal bile proteins to the perfusate.(ABSTRACT TRUNCATED AT 250 WORDS)