Tumor necrosis factor alpha increases intestinal permeability in mice with fulminant hepatic failure.

AIM: To determine the effect of tumor necrosis factor alpha (TNF-alpha) on intestinal permeability (IP) in mice with fulminant hepatic failure (FHF), and the expression of tight junction proteins. METHODS: We selected D-lactate as an index of IP, induced FHF using D-galactosamine/lipopolysaccharide and D-galactosamine/TNF-alpha, assessed the results using an enzymatic-spectrophotometric method, transmission electron microscopy, immunohistochemistry, Western blotting and real-time quantitative polymerase chain reaction. The effect of the administration of anti-TNF-alpha immunoglobulin G (IgG) antibody, before the administration of D-galactosamine/lipopolysaccharide, on TNF-alpha was also assessed. RESULTS: IP was significantly increased in the mouse model of FHF 6 h after injection (13.57 +/- 1.70 mg/L, 13.02 +/- 1.97 mg/L vs 3.76 +/- 0.67 mg/L, P = 0.001). Electron microscopic analysis revealed tight junction (TJ) disruptions, epithelial cell swelling, and atrophy of intestinal villi. Expression of occludin and claudin-1 mRNA was significantly decreased in both FHF models (occludin: 0.57 +/- 0.159 fold vs baseline, P = 0.000; claudin-1: 0.3067 +/- 0.1291 fold vs baseline, P = 0.003), as were the distribution density of proteins in the intestinal mucosa and the levels of occludin and claudin-1 protein (occludin: 0.61 +/- 0.0473 fold vs baseline, P = 0.000; claudin-1: 0.6633 +/- 0.0328 fold vs baseline, P = 0.000). Prophylactic treatment with anti-TNF-alpha IgG antibody prevented changes in IP (4.50 +/- 0.97 mg/L vs 3.76 +/- 0.67 mg/L, P = 0.791), intestinal tissue ultrastructure, and the mRNA levels of occludin and claudin-1 expression (occludin: 0.8865 +/- 0.0274 fold vs baseline, P = 0.505; claudin-1: 0.85 +/- 0.1437 fold vs baseline, P = 0.1), and in the protein levels (occludin: 0.9467 +/- 0.0285 fold vs baseline, P > 0.05; claudin-1: 0.9533 +/- 0.0186 fold vs baseline, P = 0.148). CONCLUSION: Increased in IP stemmed from the downregulation of the TJ proteins occludin and claudin-1, and destruction of the TJ in the colon, which were induced by TNF-alpha in FHF mice. (c) 2012 Baishideng. All rights reserved.