p-Nitrophenol hydroxylation. A microsomal oxidation which is highly inducible by ethanol.
p-Nitrophenol is widely employed as a substrate for the study of the glucuronide and sulfate conjugation pathways. However, in perfused livers from ethanol-treated rats, p-nitrophenol was rapidly metabolized to 4-nitrocatechol. The 4-nitrocatechol formed competed with p-nitrophenol for conjugation with glucuronic acid and sulfate, and interfered with the direct spectral measurement of p-nitrophenol. In isolated microsomes, rates of p-nitrophenol hydroxylation were increased 6-fold after chronic ethanol treatment. Much smaller induction was observed after pretreatment of rats with phenobarbital (70% increase) or beta-naphthoflavone (30% increase). In addition, the 6-fold increase in rates of p-nitrophenol hydroxylation after chronic ethanol treatment was greater than increases in activity observed for the microsomal metabolism of aniline, 7-ethoxycoumarin, benzo(a)pyrene, ethanol, or aminopyrine. These data demonstrate that p-nitrophenol may be an extremely useful substrate for the study of changes in drug-metabolizing activity induced by ethanol treatment.
Reinke
L A
LA
Moyer
M J
MJ
D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006900:Hydroxylation; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000378:metabolism*; D009596:Nitrophenols / Q000378:metabolism*; D010084:Oxidation-Reduction; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D009596:Nitrophenols; D000431:Ethanol; D019324:beta-Naphthoflavone; C024836:4-nitrophenol; D010634:Phenobarbital