Reductive metabolism of 4-nitrobiphenyl by rat liver fraction

Abstract

The metabolites of 4-nitrobiphenyl (4-NBP) mere studied using S-9 under anaerobic conditions. Ten metabolites mere isolated and tentatively identified by high-performance liquid chromatography/atmospheric pressure chemical ionization/mass spectrometry (HPLC/APCI/MS), which is a novel efficient technqiue for analyses of metabolites, HPLC retention times and UV spectra have been also used for the confirmation, Among them, 4-aminobiphenyl (4-ABP, 79% of total metabolites) and hydroxylaminobiphenyls were found to be the major metabolites, and 4-acetylaminobiphenyl (4-AABP), N-hydroxy-4-acetylaminobiphenyl (4-AABP-N-OH), x-OH-4-nitrobiphenyl biphenylene and N-formyl-4-aminobiphenyl (N-formyl-4-ABP) were the minor metabolites, Based on the metabolities identified, different metabolic pathways of 4-NBP in rat liver, including N-hydroxylation, N-acetylation, N-formylation, de-nitro-group biotransformation and ring hydroxylation mere proposed to elucidate the mechanisms of toxification and detoxification, In addition, experimental conditions such as incubation time and S-9 amounts were optimized