Elsevier

Toxicology Letters

Volume 90, Issues 2–3, 7 February 1997, Pages 207-216
Toxicology Letters

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

https://doi.org/10.1016/S0378-4274(96)03857-XGet rights and content
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Abstract

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 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.

Keywords

CYP2B expression
Nitric oxide
Rat

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