Abstract
Phenobarbital, the potent inducer of CYP2B and CYP3A, and dexamethasone, that induces CYP3A, are not able to elevate p-nitrophenol hydroxylase activity of CYP2E1. However, rats treated with phenobarbital and dexamethasone 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 required for the induction. 3-amino-1,2,4-triazole and anti CYP2E1 IgG inhibition studies show that CYP2E1 is not responsible for enhanced p-nitrophenol hydroxylation, but the residual activity indicates the participation of other isozyme(s). As a result of double induction, changes in the amount of CYP2E1 of microsomes were not detected by Western blot analysis compared to untreated rat liver microsomes.
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