Ketamine-induced gastroprotection during endotoxemia: role of heme-oxygenase-1

Dig Dis Sci. 2006 Sep;51(9):1571-81. doi: 10.1007/s10620-005-9013-0. Epub 2006 Aug 22.


Inducible nitric oxide synthase contributes to lipopolysacharide-induced gastric injury. In contrast, heme-oxygenase-1 has anti-inflammatory effects and is protective against oxidative tissue injury. Ketamine attenuates injury from lipopolysacharide and is associated with changes in oxidative stress proteins, but its effects on the stomach remain to be fully elucidated. We hypothesized that ketamine would diminish gastric injury from lipopolysacharide via down-regulation of nuclear factor-kappass, activator protein-1, and inducible nitric oxide synthase, as well as up-regulation of heme-oxygenase-1. Ketamine up-regulated heme-oxygenase-1 and attenuated lipopolysacharide-induced changes in gastric nuclear factor-kappass, activator protein-1, and inducible nitric oxide synthase. Ketamine negated LPS-induced gastric injury from acidified ethanol, an effect reversed by tin protoporphorin IX. Ketamine diminishes the susceptibility of gastric mucosa to damage from luminal irritants during endotoxemia, which is mediated in part by down-regulation of iNOS and up-regulation of HO-1.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Analysis of Variance
  • Anesthetics, Dissociative / pharmacology*
  • Animals
  • Blotting, Western
  • Endotoxemia / drug therapy*
  • Endotoxemia / enzymology
  • Ethanol / pharmacology
  • Female
  • Gastric Mucosa / drug effects*
  • Gastric Mucosa / enzymology
  • Heme Oxygenase-1 / metabolism*
  • Ketamine / pharmacology*
  • Lipopolysaccharides / pharmacology
  • NF-kappa B / drug effects
  • NF-kappa B / metabolism
  • Nitric Oxide Synthase Type II / antagonists & inhibitors
  • Nitric Oxide Synthase Type II / drug effects
  • Nitric Oxide Synthase Type II / metabolism
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factor AP-1 / drug effects
  • Transcription Factor AP-1 / metabolism


  • Anesthetics, Dissociative
  • Lipopolysaccharides
  • NF-kappa B
  • RNA, Messenger
  • Transcription Factor AP-1
  • Ethanol
  • Ketamine
  • Nitric Oxide Synthase Type II
  • Heme Oxygenase-1