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 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.
Damme
B
B
Institute of Environmental Toxicology, Martin Luther University, Halle, Germany.
Darmer
D
D
Pankow
D
D
D000818:Animals; D001241:Aspirin / Q000633:toxicity*; D015152:Blotting, Northern; D003513:Cycloheximide / Q000494:pharmacology; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D003609:Dactinomycin / Q000494:pharmacology; D004790:Enzyme Induction; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009596:Nitrophenols / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D012980:Sodium Salicylate / Q000633:toxicity*; D015533:Transcriptional Activation
D009596:Nitrophenols; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D003609:Dactinomycin; D003577:Cytochrome P-450 Enzyme System; D003513:Cycloheximide; D006899:Mixed Function Oxygenases; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating; D001241:Aspirin; D012980:Sodium Salicylate