Abstract
Administration of recombinant human interleukin-1 alpha to adult male rats caused a significant reduction in the levels of hepatic cytochrome P450 and P450 reductase activity at 24 h after the treatment. The mRNAs for cytochrome P450 1A2 and 2E1 were reduced more than 70% at 12 h after administration of interleukin-1 alpha and remained decreased even after 48 h. By contrast, cytochrome P450 2C11 mRNA was reduced only by 30% at 12 h after the treatment and returned to the control levels by 48 h, suggesting that interleukin-1 alpha has a differential effect on the expression of P450 mRNAs. Aniline hydroxylase, benzphetamine N-demethylase and 7-ethoxycoumarin O-deethylase activities were significantly decreased at 24 h after interleukin-1 alpha treatment. The proteins for cytochrome P450 1A2 and 2E1 were reduced by about 50% at 24 h after interleukin-1 alpha treatment.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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7-Alkoxycoumarin O-Dealkylase / metabolism
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Aniline Hydroxylase / metabolism
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Animals
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Blotting, Northern
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Blotting, Western
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Cytochrome P-450 CYP1A2 / genetics
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Cytochrome P-450 CYP1A2 / metabolism
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Cytochrome P-450 CYP2E1 / genetics
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Cytochrome P-450 CYP2E1 / metabolism
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Cytochrome P-450 Enzyme System / genetics
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Cytochrome P-450 Enzyme System / metabolism*
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Electrophoresis, Polyacrylamide Gel
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Humans
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Interleukin-1 / administration & dosage
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Interleukin-1 / pharmacology
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Interleukin-1 / toxicity*
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Male
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Microsomes, Liver / drug effects*
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Microsomes, Liver / enzymology
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NADH, NADPH Oxidoreductases / genetics
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NADH, NADPH Oxidoreductases / metabolism*
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NADPH-Ferrihemoprotein Reductase
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Oxidoreductases, N-Demethylating / metabolism
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RNA, Messenger / biosynthesis
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Rats
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Rats, Sprague-Dawley
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Recombinant Proteins / administration & dosage
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Recombinant Proteins / pharmacology
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Recombinant Proteins / toxicity*
Substances
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Interleukin-1
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RNA, Messenger
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Recombinant Proteins
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Cytochrome P-450 Enzyme System
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7-Alkoxycoumarin O-Dealkylase
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Cytochrome P-450 CYP2E1
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Aniline Hydroxylase
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Cytochrome P-450 CYP1A2
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benzphetamine N-demethylase
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Oxidoreductases, N-Demethylating
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NADH, NADPH Oxidoreductases
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NADPH-Ferrihemoprotein Reductase