Experimental colitis increases small intestine permeability in the rat

Walter Fries, Emanuela Mazzon, Stefano Squarzoni, Alessandro Martin, Diego Martines, Antonio Micali, Giacomo Carlo Sturniolo, Sandra Citi, Giuseppe Longo

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Abstract

Small intestine permeability is frequently altered in patients with Crohn's disease and is thought to play a pathogenic role. The aim of this study was to investigate the permeability and structure of small intestine tight junctions (TJ) in an animal model of chronic distal colitis. Seven days after colitis induction with trinitrobenzenesulfonic acid/ethanol, the duodenal and ileal TJ were studied by means of transmission electron microscopy using lanthanum nitrate, freeze fractures, and immunohistochemistry of occludin, ZO-1, and cingulin. Animals treated with intrarectal ethanol alone served as controls. In controls, 7.5% of duodenal and 9.6% of ileal TJ were permeable to lanthanum, whereas in colitis, permeability increased significantly (79.5% and 72.9%, respectively; p <0.001, both segments compared with controls). In colitis, the percentage of 'leaky' junctions in duodena as well as in terminal ilea correlated positively with the macroscopic colon damage score (p <0.02 and p <0.005, respectively). Freeze-fracture analysis and immunohistochemistry of cingulin and ZO-1 did not reveal any difference between control and treated animals, whereas the signal of the transmembrane protein occludin was found to be disrupted and irregular in both small intestine segments. Distal colitis induces an increase of TJ permeability throughout the entire small intestine, and the extent of alterations correlates with colonic damage. Alterations in the transmembrane protein occludin seem to be responsible for the observed changes. Further investigation is needed to elucidate the mechanism of TJ alterations by a remote focus of inflammation.

Original languageEnglish
Pages (from-to)49-57
Number of pages9
JournalLaboratory Investigation
Volume79
Issue number1
Publication statusPublished - Jan 1999

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Fries, W., Mazzon, E., Squarzoni, S., Martin, A., Martines, D., Micali, A., Sturniolo, G. C., Citi, S., & Longo, G. (1999). Experimental colitis increases small intestine permeability in the rat. Laboratory Investigation, 79(1), 49-57.