Inducible nitric oxide synthase and tumor necrosis factor-alpha in delayed gastric emptying and gastrointestinal transit induced by lipopolysaccharide in mice.

Abstract

Gastrointestinal motility disturbances during endotoxemia are probably caused by lipopolysaccharide (LPS)-induced factors: candidates include nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), interleukin-1ss, and interleukin-6. Flow cytometry was used to determine the effects of LPS and these factors on gastric emptying (evaluated indirectly by determining percent gastric retention; %GR) and gastrointestinal transit (GIT) in male BALB/c mice (23-28 g). NO (300 microg/mouse, N = 8) and TNF-alpha (2 microg/mouse, N = 7) increased (P < 0.01) GR and delayed GIT, mimicking the effect of LPS (50 microg/mouse). During early endotoxemia (1.5 h after LPS), inhibition of inducible NO synthase (iNOS) by a selective inhibitor, 1400 W (150 microg/mouse, N = 11), but not antibody neutralization of TNF-alpha (200 microg/mouse, N = 11), reversed the increase of GR (%GR 78.8 +/- 3.3 vs 47.2 +/- 7.5%) and the delay of GIT (geometric center 3.7 +/- 0.4 vs 5.6 +/- 0.2). During late endotoxemia (8 h after LPS), both iNOS inhibition (N = 9) and TNF-alpha neutralization (N = 9) reversed the increase of GR (%GR 33.7 +/- 2.0 vs 19.1 +/- 2.6% (1400 W) and 20.1 +/- 2.0% (anti-TNF-alpha)), but only TNF-alpha neutralization reversed the delay of GIT (geometric center 3.9 +/- 0.4 vs 5.9 +/- 0.2). These findings suggest that iNOS, but not TNF-alpha, is associated with delayed gastric emptying and GIT during early endotoxemia and that during late endotoxemia, both factors are associated with delayed gastric emptying, but only TNF-alpha is associated with delayed GIT.

• Authors: T Inada, N Hamano, M Yamada, A Shirane, K Shingu
• Journal: Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas (Braz J Med Biol Res) Vol. 39 Issue 11 Pg. 1425-34 (Nov 2006) ISSN: 0100-879X [Print] Brazil
• PMID: 17146555 (Publication Type: Journal Article)

Chemical References

• Interleukin-1beta
• Interleukin-6
• Lipopolysaccharides
• Tumor Necrosis Factor-alpha
• Nitric Oxide Synthase Type II

Topics

• Animals
• Blotting, Western
• Disease Models, Animal
• Endotoxemia (physiopathology)
• Enzyme-Linked Immunosorbent Assay
• Flow Cytometry
• Gastric Emptying (drug effects, physiology)
• Gastrointestinal Transit (drug effects, physiology)
• Interleukin-1beta (metabolism)
• Interleukin-6 (metabolism)
• Lipopolysaccharides (pharmacology)
• Male
• Mice
• Mice, Inbred BALB C
• Nitric Oxide Synthase Type II (drug effects, metabolism)
• Tumor Necrosis Factor-alpha (drug effects, metabolism)