Differential effect of interleukin-1 alpha on rat hepatic cytochrome P450 monooxygenases

Toxicology. 1996 Nov 15;114(1):37-46. doi: 10.1016/s0300-483x(96)03475-0.

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

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 7-Alkoxycoumarin O-Dealkylase / metabolism
  • Aniline Hydroxylase / metabolism
  • Animals
  • Blotting, Northern
  • Blotting, Western
  • Cytochrome P-450 CYP1A2 / genetics
  • Cytochrome P-450 CYP1A2 / metabolism
  • Cytochrome P-450 CYP2E1 / genetics
  • Cytochrome P-450 CYP2E1 / metabolism
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism*
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Interleukin-1 / administration & dosage
  • Interleukin-1 / pharmacology
  • Interleukin-1 / toxicity*
  • Male
  • Microsomes, Liver / drug effects*
  • Microsomes, Liver / enzymology
  • NADH, NADPH Oxidoreductases / genetics
  • NADH, NADPH Oxidoreductases / metabolism*
  • NADPH-Ferrihemoprotein Reductase
  • Oxidoreductases, N-Demethylating / metabolism
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / toxicity*

Substances

  • Interleukin-1
  • RNA, Messenger
  • Recombinant Proteins
  • Cytochrome P-450 Enzyme System
  • 7-Alkoxycoumarin O-Dealkylase
  • Cytochrome P-450 CYP2E1
  • Aniline Hydroxylase
  • Cytochrome P-450 CYP1A2
  • benzphetamine N-demethylase
  • Oxidoreductases, N-Demethylating
  • NADH, NADPH Oxidoreductases
  • NADPH-Ferrihemoprotein Reductase