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Ursodeoxycholic Acid Ameliorates Experimental Ileitis Counteracting Intestinal Barrier Dysfunction and Oxidative Stress

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Abstract

The aim of this study was to evaluate the effect of ursodeoxycholic acid (UDCA) on intestinal permeability (IP) and reactive oxygen species (ROS) generation in indomethacin-induced enteropathy, a well-known experimental model of Crohn's disease. Seventy-eight male Wistar rats were randomly assigned to receive indomethacin, indomethacin + UDCA, or vehicles. Indomethacin induced a significant increase in the fraction of urinary excretion of 51Cr-EDTA following oral administration (7.9 ± 1.3 vs 2.3 ± 0.2%; P < 0.05) and lucigenin-amplified chemiluminescence in intestinal fragments ex vivo (10.1 ± 1.9 vs 2.6 ± 0.4 cpm × 103/mg; P < 0.05) compared to controls. UDCA significantly reversed these effects (P < 0.05), without being incorporated in biliary bile acid composition (HPLC analysis). These findings support a local protective effect of UDCA in experimental ileitis by the modulation of intestinal barrier dysfunction and oxidative stress. In short, they provide insights into mechanisms of action of UDCA in intestinal inflammation and a new perspective on the treatment of Crohn's disease.

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Authors and Affiliations

  1. Department of Gastroenterology (Laboratory of Investigative Medicine 07), School of Medicine, University of São Paulo, São Paulo, Brazil

    Carlos Felipe Bernardes-Silva, Adérson O. M. C. Damião, Aytan M. Sipahi, Fabio P. Lopasso, Maria Laura L. Lordello, Carmem L. O. Agostinho & Antonio A. Laudanna

  2. Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil

    Francisco R. M. Laurindo

  3. Department of Pathology, School of Medicine, University of São Paulo, São Paulo, Brazil

    Kiyoshi Iriya & Carlos A. Buchpiguel

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  1. Carlos Felipe Bernardes-Silva
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Bernardes-Silva, C.F., Damião, A.O.M.C., Sipahi, A.M. et al. Ursodeoxycholic Acid Ameliorates Experimental Ileitis Counteracting Intestinal Barrier Dysfunction and Oxidative Stress. Dig Dis Sci 49, 1569–1574 (2004). https://doi.org/10.1023/B:DDAS.0000043365.39251.6e

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