The effect of phenobarbital and beta-naphthoflavone induction on the metabolism of biphenyl in the rat and mouse.
The effects of induction by beta-naphthoflavone (BNF) and by phenobarbital (PB) on the metabolism of biphenyl were studied in the rat (Sprague-Dawley) and the mouse (C57BL/6Tex and DBA/2Tex). Marked changes were observed after BNF induction. A major pathway of metabolism in C57BL/6 mice after induction was biphenyl leads to 2-hydroxybiphenyl leads to 2,5-dihydroxybiphenyl. This formerly minor pathways replaced biphenyl leads to 4-hydroxybiphenyl as the chief pathway of metabolism. No effect was observed in DBA/2 mice, in accord with observations that these animals lack the cytosolic receptor needed for cytochrome P1-450 induction. In Sprague-Dawley rats, the effect of BNF induction was to increase greatly the biphenyl leads to 4-hydroxybiphenyl leads to 3,4-dihydroxybiphenyl pathway and to decrease the 4-hydroxy leads to 4,4'-dihydroxy conversion. The effects of PB induction were less striking. Both genetic strains of mice showed a slight increase in 4,4'-dihydroxybiphenyl formation, and a slight decrease in 3,4-dihydroxybiphenyl formation. In the Sprague-Dawley rat, a slight increase in hydroxylation leading to 3-hydroxybiphenyl was observed. 2-Hydroxylation of biphenyl was not a specific feature of cytochrome P1-450 induction. The formation of the 2,5-diol as a major product was characteristic of cytochrome P1-450 induction in the C57BL/6 mouse, but not in the Sprague-Dawley rat. In both the mouse and rat, cytochrome P1-450 induction led to second-stage oxidation in the aromatic ring that was oxidized in the first stage, but the major pathways after induction were not in the same in both species.
D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D008297:Male; D051379:Mice; D010084:Oxidation-Reduction; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D013045:Species Specificity; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D001713:Biphenyl Compounds; D005419:Flavonoids; D019324:beta-Naphthoflavone; D010634:Phenobarbital