Evidence for nitric oxide participation in down-regulation of CYP2B1/2 gene expression at the pretranslational level

Toxicol Lett. 1997 Feb 7;90(2-3):207-16. doi: 10.1016/s0378-4274(96)03857-x.


Septic or inflammatory stimuli suppress drug metabolism by cytochrome P-450 in the liver, presumably at the pretranslational level. We have shown previously that nitric oxide is responsible at least in part for the inhibition by bacterial lipopolysaccharide of phenobarbital-induced CYP2B1/2 activity in vivo. This was attributed to the interaction of nitric oxide with heme in the active-center of cytochrome P450, leading to enzyme inactivation. Here, we report that endogeneous nitric oxide also contributes to LPS-induced suppression of CYP2B1/2 in vivo by down-regulating the expression of CYP2B1/2 protein and mRNA.

MeSH terms

  • Animals
  • Aryl Hydrocarbon Hydroxylases*
  • Cytochrome P-450 CYP2B1 / drug effects
  • Cytochrome P-450 CYP2B1 / genetics*
  • Cytochrome P-450 Enzyme System / drug effects
  • Cytochrome P-450 Enzyme System / genetics*
  • Down-Regulation / drug effects*
  • Gene Expression Regulation / drug effects*
  • Male
  • Nitric Oxide / physiology*
  • Protein Biosynthesis / drug effects*
  • Rats
  • Rats, Wistar
  • Steroid Hydroxylases / drug effects
  • Steroid Hydroxylases / genetics*


  • Nitric Oxide
  • Cytochrome P-450 Enzyme System
  • Steroid Hydroxylases
  • Aryl Hydrocarbon Hydroxylases
  • Cytochrome P-450 CYP2B1
  • steroid 16-beta-hydroxylase