Ketamine-induced gastroprotection during endotoxemia: role of heme-oxygenase-1.
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.
Helmer
Kenneth S
KS
Department of Surgery, University of Texas Medical School, Houston, Texas 77026, USA.
Suliburk
James W
JW
Mercer
David W
DW
D000704:Analysis of Variance; D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D019446:Endotoxemia / Q000188:drug therapy* / Q000201:enzymology; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D007649:Ketamine / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000187:drug effects / Q000378:metabolism
D000778:Anesthetics, Dissociative; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D000431:Ethanol; D007649:Ketamine; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1