THE EFFECT OF PHENOBARBITAL AND DEXAMETHASONE COADMINISTRATION ON THEACTIVITY OF RAT-LIVER P450 SYSTEM

Phenobarbital, the potent inducer of CYP2B and CYP3A, and dexamethason e, that induces CYP3A, are not able to elevate p-nitrophenol hydroxyla se activity of CYP2E1. However, rats treated with phenobarbital and de xamethasone in combination showed threefold increase in p-nitrophenol hydroxylation and the activity correlates with an elevated amount of a 53.000 dalton protein. Biosynthesis of mRNA and P450 protein is requi red for the induction. 3-amino-1,2,4-triazole and anti CYP2E1 IgG inhi bition studies show that CYP2E1 is not responsible for enhanced p-nitr ophenol hydroxylation, but the residual activity indicates the partici pation of other isozyme(s). As a result of double induction, changes i n the amount of CYP2E1 of microsomes were not detected by Western blot analysis compared to untreated rat liver microsomes. (C) 1994 Academi c Press, Inc.