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, H. R. Ford

Research output: Contribution to journalArticle

59 Scopus citations

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)
Pages (from-to)G173-G181
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume281
Issue number1 44-1
StatePublished - Oct 11 2001
Externally publishedYes

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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. R. (2001). Scavenging nitric oxide reduces hepatocellular injury after endotoxin challenge. American Journal of Physiology - Gastrointestinal and Liver Physiology, 281(1 44-1), G173-G181.