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Ketamine-Induced Gastroprotection During Endotoxemia: Role of Heme-Oxygenase-1

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Abstract

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-κß, 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-κß, 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.

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Acknowledgments

The authors gratefully acknowledge the expert assistance of Lily Chang, BS, and Yan Cui, MD. We also acknowledge the expertise of the Quantitative Genomics Core Laboratory, Department of Integrative Biology & Physiology, The University of Texas Health Science Center—Houston, for performing the quantitative real-time RT-PCR.

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Authors and Affiliations

  1. Department of Surgery, University of Texas Medical School, Houston, Texas, USA

    Kenneth S. Helmer, James W. Suliburk & David W. Mercer

  2. UT-Houston Medical School/LBJ General Hospital, 5656 Kelley Street, Suite 3-OS 62008, Houston, Texas, 77026, USA

    David W. Mercer

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  1. Kenneth S. Helmer
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  2. James W. Suliburk
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  3. David W. Mercer
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Correspondence to David W. Mercer.

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This work was supported by NIGMS Grants GM-38529 and GM-08792.

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Helmer, K.S., Suliburk, J.W. & Mercer, D.W. Ketamine-Induced Gastroprotection During Endotoxemia: Role of Heme-Oxygenase-1. Dig Dis Sci 51, 1571–1581 (2006). https://doi.org/10.1007/s10620-005-9013-0

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