Scavenging nitric oxide reduces hepatocellular injury after endotoxin challenge

E. P. Nadler, E. C. Dickinson, D. Beer-Stolz, S. M. Alber, S. C. Watkins, D. W. Pratt, Henri Ford

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Sustained upregulation of inducible nitric oxide (NO) synthase in the liver after endotoxin [lipopolysaccharide (LPS)] challenge may result in hepatocellular injury. We hypothesized that administration of a NO scavenger, NOX, may attenuate LPS-induced hepatocellular injury. Sprague-Dawley rats received NOX or saline via subcutaneous osmotic pumps, followed 18 h later by LPS challenge. Hepatocellular injury was assessed using biochemical assays, light, and transmission electron microscopy (TEM). Interleukin (IL)-6 mRNA was measured by RT-PCR. Tumor necrosis factor (TNF)-α protein expression was determined by immunohistochemistry. NOX significantly reduced serum levels of ornithine carbamoyltransferase and aspartate aminotransferase. TNF-α and IL-6 expression were increased in the livers of saline-treated but not NOX-treated rats. Although there was no difference between groups by light microscopy, TEM revealed obliteration of the space of Disse in saline-treated but not in NOX-treated animals. Electron paramagnetic resonance showed the characteristic mononitrosyl complex in NOX-treated rats. We conclude that NOX reduces hepatocellular injury after endotoxemia. NOX may be useful in the management of hepatic dysfunction secondary to sepsis or other diseases associated with excessive NO production.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume281
Issue number1 44-1
StatePublished - Oct 11 2001
Externally publishedYes

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Endotoxins
Nitric Oxide
Lipopolysaccharides
Wounds and Injuries
Transmission Electron Microscopy
Liver
Interleukin-6
Tumor Necrosis Factor-alpha
Ornithine-Oxo-Acid Transaminase
Ornithine Carbamoyltransferase
Light
Endotoxemia
Electron Spin Resonance Spectroscopy
Nitric Oxide Synthase Type II
Aspartate Aminotransferases
Sprague Dawley Rats
Microscopy
Sepsis
Up-Regulation
Immunohistochemistry

Keywords

  • Dithiocarbamate
  • Endotoxemia
  • Inducible nitric oxide synthase
  • Interleukin-6
  • Ornithine carbamoyltransferase

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

Nadler, E. P., Dickinson, E. C., Beer-Stolz, D., Alber, S. M., Watkins, S. C., Pratt, D. W., & Ford, H. (2001). Scavenging nitric oxide reduces hepatocellular injury after endotoxin challenge. American Journal of Physiology - Gastrointestinal and Liver Physiology, 281(1 44-1).

Scavenging nitric oxide reduces hepatocellular injury after endotoxin challenge. / Nadler, E. P.; Dickinson, E. C.; Beer-Stolz, D.; Alber, S. M.; Watkins, S. C.; Pratt, D. W.; Ford, Henri.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 281, No. 1 44-1, 11.10.2001.

Research output: Contribution to journalArticle

Nadler, EP, Dickinson, EC, Beer-Stolz, D, Alber, SM, Watkins, SC, Pratt, DW & Ford, H 2001, 'Scavenging nitric oxide reduces hepatocellular injury after endotoxin challenge', American Journal of Physiology - Gastrointestinal and Liver Physiology, vol. 281, no. 1 44-1.
Nadler EP, Dickinson EC, Beer-Stolz D, Alber SM, Watkins SC, Pratt DW et al. Scavenging nitric oxide reduces hepatocellular injury after endotoxin challenge. American Journal of Physiology - Gastrointestinal and Liver Physiology. 2001 Oct 11;281(1 44-1).
Nadler, E. P. ; Dickinson, E. C. ; Beer-Stolz, D. ; Alber, S. M. ; Watkins, S. C. ; Pratt, D. W. ; Ford, Henri. / Scavenging nitric oxide reduces hepatocellular injury after endotoxin challenge. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2001 ; Vol. 281, No. 1 44-1.
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