title: The effect of phenobarbital and dexamethasone coadministration on the activity of rat liver P450 system.
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.
authors.affiliation: Central Research Institute for Chemistry, Hungarian Academy of Sciences, Budapest.
authors.forename: K
authors.initials: K
authors.lastname: Monostory
authors.forename: L
authors.initials: L
authors.lastname: Vereczkey
mesh_terms: D000633:Aminopyrine N-Demethylase / Q000096:biosynthesis; D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004347:Drug Interactions; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction; D005037:Ethylmorphine-N-Demethylase / Q000096:biosynthesis; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D003609:Dactinomycin; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; D003513:Cycloheximide; D000633:Aminopyrine N-Demethylase; D005037:Ethylmorphine-N-Demethylase; D010634:Phenobarbital