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

• Published in: Brazilian journal of medical and biological research Vol. 39; no. 11; pp. 1425 - 1434
• Main Authors: Inada, T, Hamano, N, Yamada, M, Shirane, A, Shingu, K
• Format: Journal Article
• Language: English; Portuguese
• Published: Brazil Associação Brasileira de Divulgação Científica 01.11.2006
• Subjects: Animals; BIOLOGY; Blotting, Western; Disease Models, Animal; Endotoxemia - physiopathology; Endotoxin; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Gastric emptying; Gastric Emptying - drug effects; Gastric Emptying - physiology; Gastrointestinal transit; Gastrointestinal Transit - drug effects; Gastrointestinal Transit - physiology; Inducible nitric oxide synthase; Interleukin-1beta - metabolism; Interleukin-6 - metabolism; Lipopolysaccharide; Lipopolysaccharides - pharmacology; Male; MEDICINE, RESEARCH & EXPERIMENTAL; Mice; Mice, Inbred BALB C; Nitric Oxide Synthase Type II - drug effects; Nitric Oxide Synthase Type II - metabolism; Tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - drug effects; Tumor Necrosis Factor-alpha - metabolism; Gastrointestinal transit; Lipopolysaccharide; Gastric emptying; Tumor necrosis factor-alpha; Endotoxin; Inducible nitric oxide synthase
• ISSN: 0100-879X; 1414-431X; 1414-431X; 0100-879X
• DOI: 10.1590/s0100-879x2006001100006

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.