Induction of hepatic cytochrome P4502E1 in rats by acetylsalicylic acid or sodium salicylate

Studies were conducted on the mechanism of the ethanol-inducible cytochrome P450 (cytochrome P4502E1, CYP 2E1) induction by acetylsalicylic acid (ASA) or its metabolite salicylate (SAL). Many exogenous inducers of CYP 2E1 seem to increase CYP 2E1 by post-transcriptional activation without elevation...

Full description

Saved in:
Bibliographic Details
Published in:Toxicology (Amsterdam) 1996-01, Vol.106 (1), p.99-103
Main Authors: Damme, Britt, Darmer, Dorothea, Pankow, Dieter
Format: Article
Language:English
Subjects:
Acetylsalicylic acid
Analgesics
Animals
Aspirin - toxicity
Biological and medical sciences
Blotting, Northern
Cycloheximide - pharmacology
CYP 2E1
CYP 2E1 mRNA
Cytochrome P-450 CYP2E1
Cytochrome P-450 Enzyme System - biosynthesis
Dactinomycin - pharmacology
Enzyme Induction
Liver - drug effects
Liver - enzymology
Male
Medical sciences
Microsomes, Liver - drug effects
Microsomes, Liver - enzymology
Mixed Function Oxygenases - metabolism
Neuropharmacology
Nitrophenols - metabolism
Oxidoreductases, N-Demethylating - biosynthesis
Pharmacology. Drug treatments
Protein Synthesis Inhibitors - pharmacology
Rats
Rats, Wistar
RNA, Messenger - biosynthesis
Salicylate
Sodium Salicylate - toxicity
Transcriptional Activation
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Studies were conducted on the mechanism of the ethanol-inducible cytochrome P450 (cytochrome P4502E1, CYP 2E1) induction by acetylsalicylic acid (ASA) or its metabolite salicylate (SAL). Many exogenous inducers of CYP 2E1 seem to increase CYP 2E1 by post-transcriptional activation without elevation of its mRNA level. Administration of a single high dose of ASA or SAL produces a significant increase in the activity of the hepatic microsomal p-nitrophenol hydroxylase in rats. Pretreatment of ASA-treated rats with a blocker of mRNA transcription, actinomycin D, or a blocker of protein synthesis, cycloheximide, markedly suppressed this enhanced activity of microsomal p-nitrophenol hydroxylase. The CYP 2E1 mRNA levels in livers of control rats and rats treated with ASA or SAL were measured by Northern blot analysis. Significantly elevated CYP 2E1 mRNA levels were measured in livers of treated rats compared with mRNA amounts of the control group. These data suggest that mRNA elevation seems to be characteristic for ASA induction, while other inducing agents show different patterns and mechanisms of activation.
ISSN:0300-483X
1879-3185
DOI:10.1016/0300-483X(95)03168-F