Combined action of phenobarbital and dexamethasone on the activity of rat liver P450 system

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Abstract

Phenobarbital and dexamethasone are potent inducers of the same cytochrome P450 form, CYP3A1, but the mechanism of action is not quite clear. If the mechanism of induction by phenobarbital and dexamethasone is different, additive effect may be observed in the specific actitivies of CYP3A1: ethylmorphine or aminopyrine N-demethylation of liver microsomes from rats treated with phenobarbital and dexamethasone in combination. The results of recent work could not display differences in CYP3A1 activities between the groups of animals single-administered and coadministered with phenobarbital and dexamethasone. However, p-nitrophenol hydroxylation suprisingly increased threefold as a result of double induction. 3-amino-1,2,4-triazole inhibition study shows that CYP2E1 is responsible for 60% of enhanced p-nitrophenol hydroxylase activity, but the residual 40% indicates the participation of other isoenzyme(s).

Original languageEnglish
Pages (from-to)296-300
Number of pages5
JournalActa Pharmaceutica Hungarica
Volume63
Issue number5
Publication statusPublished - 1993

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Phenobarbital
Dexamethasone
Liver
Ethylmorphine
Amitrole
Aminopyrine
Cytochrome P-450 CYP2E1
Liver Microsomes
Hydroxylation
Mixed Function Oxygenases
Cytochrome P-450 Enzyme System
Isoenzymes
4-nitrophenol

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

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abstract = "Phenobarbital and dexamethasone are potent inducers of the same cytochrome P450 form, CYP3A1, but the mechanism of action is not quite clear. If the mechanism of induction by phenobarbital and dexamethasone is different, additive effect may be observed in the specific actitivies of CYP3A1: ethylmorphine or aminopyrine N-demethylation of liver microsomes from rats treated with phenobarbital and dexamethasone in combination. The results of recent work could not display differences in CYP3A1 activities between the groups of animals single-administered and coadministered with phenobarbital and dexamethasone. However, p-nitrophenol hydroxylation suprisingly increased threefold as a result of double induction. 3-amino-1,2,4-triazole inhibition study shows that CYP2E1 is responsible for 60{\%} of enhanced p-nitrophenol hydroxylase activity, but the residual 40{\%} indicates the participation of other isoenzyme(s).",
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T1 - Combined action of phenobarbital and dexamethasone on the activity of rat liver P450 system

AU - Monostory, K.

AU - Vereczkey, L.

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AB - Phenobarbital and dexamethasone are potent inducers of the same cytochrome P450 form, CYP3A1, but the mechanism of action is not quite clear. If the mechanism of induction by phenobarbital and dexamethasone is different, additive effect may be observed in the specific actitivies of CYP3A1: ethylmorphine or aminopyrine N-demethylation of liver microsomes from rats treated with phenobarbital and dexamethasone in combination. The results of recent work could not display differences in CYP3A1 activities between the groups of animals single-administered and coadministered with phenobarbital and dexamethasone. However, p-nitrophenol hydroxylation suprisingly increased threefold as a result of double induction. 3-amino-1,2,4-triazole inhibition study shows that CYP2E1 is responsible for 60% of enhanced p-nitrophenol hydroxylase activity, but the residual 40% indicates the participation of other isoenzyme(s).

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