Differential effects of anesthetics on endotoxin-induced liver injury

James W. Suliburk, Ernest A. Gonzalez, Sasha D. Kennison, Kenneth S. Helmer, David W. Mercer, Anthony A. Meyer, Eileen M. Bulger, Hiroshi Ogura

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Background: The liver is both a source and a target of inflammatory and anti-inflammatory mediators during sepsis. The oxidative stress proteins inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1) are upregulated in the liver during sepsis but have opposite roles. Up-regulation of HO-1 has hepatoprotective effects, whereas iNOS has injurious effects to the liver. Although recent studies indicate that ketamine anesthesia has anti-inflammatory effects during sepsis, the effects of other anesthetics are unknown. We hypothesized that ketamine, but not isoflurane, would attenuate lipopolysaccharide (LPS)-induced liver injury through differential modulation of iNOS and HO-1. Methods: Adult rats were given no anesthesia (saline), continuous isoflurane inhalation, or intraperitoneal ketamine (70 mg/ kg). One hour later, saline or LPS (20 mg/kg intraperitoneally) was given for 5 hours. Rats were killed, serum prepared for determination of hepatocellular enzymes, and the liver assessed for iNOS and HO-1 by Western immunoblot. Results: LPS significantly increased serum aspartate aminotransferase levels, iNOS, and HO-1 immunoreactivity in the liver. Ketamine but not isoflurane attenuated LPS-induced liver injury, upregulated HO-1, and downregulated iNOS. Conclusion: These data indicate that anesthetics differ in their effects on the liver in a rat model of sepsis with LPS. Ketamine has hepatoprotective effects against LPS-induced liver injury that appear to be mediated, at least in part, by differential modulation of the oxidative stress proteins iNOS and HO-1. Thus, ketamine may be the anesthetic agent of choice for septic patients requiring anesthesia.

Original languageEnglish (US)
Pages (from-to)711-717
Number of pages7
JournalJournal of Trauma - Injury, Infection and Critical Care
Volume58
Issue number4
DOIs
StatePublished - Apr 1 2005

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Endotoxins
Heme Oxygenase-1
Anesthetics
Nitric Oxide Synthase Type II
Ketamine
Lipopolysaccharides
Liver
Wounds and Injuries
Isoflurane
Sepsis
Anesthesia
Heat-Shock Proteins
Oxidative Stress
Anti-Inflammatory Agents
Aspartate Aminotransferases
Serum
Inhalation
Up-Regulation
Down-Regulation
Western Blotting

Keywords

  • Anesthesia
  • Heme oxygenase-1 (HO-1)
  • Inducible nitric oxide synthase (iNOS)
  • Isoflurane
  • Ketamine
  • Lipopolysaccharide (LPS)

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine

Cite this

Differential effects of anesthetics on endotoxin-induced liver injury. / Suliburk, James W.; Gonzalez, Ernest A.; Kennison, Sasha D.; Helmer, Kenneth S.; Mercer, David W.; Meyer, Anthony A.; Bulger, Eileen M.; Ogura, Hiroshi.

In: Journal of Trauma - Injury, Infection and Critical Care, Vol. 58, No. 4, 01.04.2005, p. 711-717.

Research output: Contribution to journalArticle

Suliburk, JW, Gonzalez, EA, Kennison, SD, Helmer, KS, Mercer, DW, Meyer, AA, Bulger, EM & Ogura, H 2005, 'Differential effects of anesthetics on endotoxin-induced liver injury', Journal of Trauma - Injury, Infection and Critical Care, vol. 58, no. 4, pp. 711-717. https://doi.org/10.1097/01.TA.0000159245.60495.00
Suliburk, James W. ; Gonzalez, Ernest A. ; Kennison, Sasha D. ; Helmer, Kenneth S. ; Mercer, David W. ; Meyer, Anthony A. ; Bulger, Eileen M. ; Ogura, Hiroshi. / Differential effects of anesthetics on endotoxin-induced liver injury. In: Journal of Trauma - Injury, Infection and Critical Care. 2005 ; Vol. 58, No. 4. pp. 711-717.
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T1 - Differential effects of anesthetics on endotoxin-induced liver injury

AU - Suliburk, James W.

AU - Gonzalez, Ernest A.

AU - Kennison, Sasha D.

AU - Helmer, Kenneth S.

AU - Mercer, David W.

AU - Meyer, Anthony A.

AU - Bulger, Eileen M.

AU - Ogura, Hiroshi

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N2 - Background: The liver is both a source and a target of inflammatory and anti-inflammatory mediators during sepsis. The oxidative stress proteins inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1) are upregulated in the liver during sepsis but have opposite roles. Up-regulation of HO-1 has hepatoprotective effects, whereas iNOS has injurious effects to the liver. Although recent studies indicate that ketamine anesthesia has anti-inflammatory effects during sepsis, the effects of other anesthetics are unknown. We hypothesized that ketamine, but not isoflurane, would attenuate lipopolysaccharide (LPS)-induced liver injury through differential modulation of iNOS and HO-1. Methods: Adult rats were given no anesthesia (saline), continuous isoflurane inhalation, or intraperitoneal ketamine (70 mg/ kg). One hour later, saline or LPS (20 mg/kg intraperitoneally) was given for 5 hours. Rats were killed, serum prepared for determination of hepatocellular enzymes, and the liver assessed for iNOS and HO-1 by Western immunoblot. Results: LPS significantly increased serum aspartate aminotransferase levels, iNOS, and HO-1 immunoreactivity in the liver. Ketamine but not isoflurane attenuated LPS-induced liver injury, upregulated HO-1, and downregulated iNOS. Conclusion: These data indicate that anesthetics differ in their effects on the liver in a rat model of sepsis with LPS. Ketamine has hepatoprotective effects against LPS-induced liver injury that appear to be mediated, at least in part, by differential modulation of the oxidative stress proteins iNOS and HO-1. Thus, ketamine may be the anesthetic agent of choice for septic patients requiring anesthesia.

AB - Background: The liver is both a source and a target of inflammatory and anti-inflammatory mediators during sepsis. The oxidative stress proteins inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1) are upregulated in the liver during sepsis but have opposite roles. Up-regulation of HO-1 has hepatoprotective effects, whereas iNOS has injurious effects to the liver. Although recent studies indicate that ketamine anesthesia has anti-inflammatory effects during sepsis, the effects of other anesthetics are unknown. We hypothesized that ketamine, but not isoflurane, would attenuate lipopolysaccharide (LPS)-induced liver injury through differential modulation of iNOS and HO-1. Methods: Adult rats were given no anesthesia (saline), continuous isoflurane inhalation, or intraperitoneal ketamine (70 mg/ kg). One hour later, saline or LPS (20 mg/kg intraperitoneally) was given for 5 hours. Rats were killed, serum prepared for determination of hepatocellular enzymes, and the liver assessed for iNOS and HO-1 by Western immunoblot. Results: LPS significantly increased serum aspartate aminotransferase levels, iNOS, and HO-1 immunoreactivity in the liver. Ketamine but not isoflurane attenuated LPS-induced liver injury, upregulated HO-1, and downregulated iNOS. Conclusion: These data indicate that anesthetics differ in their effects on the liver in a rat model of sepsis with LPS. Ketamine has hepatoprotective effects against LPS-induced liver injury that appear to be mediated, at least in part, by differential modulation of the oxidative stress proteins iNOS and HO-1. Thus, ketamine may be the anesthetic agent of choice for septic patients requiring anesthesia.

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KW - Heme oxygenase-1 (HO-1)

KW - Inducible nitric oxide synthase (iNOS)

KW - Isoflurane

KW - Ketamine

KW - Lipopolysaccharide (LPS)

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