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Published in: Digestive Diseases and Sciences 9/2008

01-09-2008 | Original Paper

Protective Effect of Octreotide and Infliximab in an Experimental Model of Indomethacin-Induced Inflammatory Bowel Disease

Authors: Dídia H. Bismara Cury, José Edson Costa, Kioshi Irika, Luciana Mijji, Alessandre Garcez, Carlos Buchiguel, Ivani Silva, Aytan Sipahi

Published in: Digestive Diseases and Sciences | Issue 9/2008

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Abstract

Indomethacin administration in animals increases permeability of the small intestine, leading to inflammation that mimics Crohn’s disease. Nonsteroidal anti-inflammatory drugs increase the permeability of the intestinal epithelial barrier and should therefore be used with caution in patients with Crohn’s disease. We analyzed the protective effects of octreotide and the tumor necrosis factor-alpha inhibitor infliximab in a rat model of indomethacin-induced enterocolitis. Male Wistar rats received 20 mg of infliximab or 10 μg of octreotide 24 h prior to injection with indomethacin. Intestinal permeability was analyzed using Cr-51-ethylenediaminetetraacetic acid clearance. No microscopic or macroscopic alterations were observed in the rats receiving infliximab or octreotide, both of which increased permeability (P < 0.001 versus controls). Our macroscopic and microscopic findings might be related to the low specificity of infliximab and suggest that cytokines affect the intestinal epithelial barrier, as evidenced by the protective effect that infliximab had on the permeability parameters evaluated.
Literature
1.
go back to reference Elson CO, Sartor RB, Tennyson GS, Riddell RH (1995) Experimental models of inflammatory bowel disease. Gastroenterology 109(4):1344–1367PubMedCrossRef Elson CO, Sartor RB, Tennyson GS, Riddell RH (1995) Experimental models of inflammatory bowel disease. Gastroenterology 109(4):1344–1367PubMedCrossRef
2.
go back to reference Strober W (1985) Animal models of inflammatory bowel disease—an overview. Dig Dis Sci 30(12 Suppl):3S–10SPubMedCrossRef Strober W (1985) Animal models of inflammatory bowel disease—an overview. Dig Dis Sci 30(12 Suppl):3S–10SPubMedCrossRef
3.
go back to reference Kent TH, Cardelli RM, Stamler FW (1969) Small intestinal ulcers and intestinal flora in rats given indomethacin. Am J Pathol 54(2):237–249PubMed Kent TH, Cardelli RM, Stamler FW (1969) Small intestinal ulcers and intestinal flora in rats given indomethacin. Am J Pathol 54(2):237–249PubMed
4.
go back to reference Peeters M, Geypens B, Claus D, Nevens H, Ghoos Y, Verbeke G et al (1997) Clustering of increased small intestinal permeability in families with Crohn’s disease. Gastroenterology 113(3):802–807PubMedCrossRef Peeters M, Geypens B, Claus D, Nevens H, Ghoos Y, Verbeke G et al (1997) Clustering of increased small intestinal permeability in families with Crohn’s disease. Gastroenterology 113(3):802–807PubMedCrossRef
5.
go back to reference Ford J, Martin SW, Houston JB (1995) Assessment of intestinal permeability changes induced by nonsteroidal anti-inflammatory drugs in the rat. J Pharmacol Toxicol Methods 34(1):9–16PubMedCrossRef Ford J, Martin SW, Houston JB (1995) Assessment of intestinal permeability changes induced by nonsteroidal anti-inflammatory drugs in the rat. J Pharmacol Toxicol Methods 34(1):9–16PubMedCrossRef
6.
go back to reference Mahmud T, Somasundaram S, Sigthorsson G, Simpson RJ, Rafi S, Foster R et al (1998) Enantiomers of flurbiprofen can distinguish key pathophysiological steps of NSAID enteropathy in the rat. Gut 43(6):775–782PubMedCrossRef Mahmud T, Somasundaram S, Sigthorsson G, Simpson RJ, Rafi S, Foster R et al (1998) Enantiomers of flurbiprofen can distinguish key pathophysiological steps of NSAID enteropathy in the rat. Gut 43(6):775–782PubMedCrossRef
7.
go back to reference Bjarnason I, Zanelli G, Prouse P, Smethurst P, Smith T, Levi S et al (1987) Blood and protein loss via small-intestinal inflammation induced by non-steroidal anti-inflammatory drugs. Lancet 2(8561):711–714PubMedCrossRef Bjarnason I, Zanelli G, Prouse P, Smethurst P, Smith T, Levi S et al (1987) Blood and protein loss via small-intestinal inflammation induced by non-steroidal anti-inflammatory drugs. Lancet 2(8561):711–714PubMedCrossRef
8.
go back to reference Sartor RB (1994) Cytokines in intestinal inflammation: pathophysiological and clinical considerations. Gastroenterology 106(2):533–539PubMed Sartor RB (1994) Cytokines in intestinal inflammation: pathophysiological and clinical considerations. Gastroenterology 106(2):533–539PubMed
9.
go back to reference Bertrand V, Guimbaud R, Tulliez M, Mauprivez C, Sogni P, Couturier D et al (1998) Increase in tumor necrosis factor-alpha production linked to the toxicity of indomethacin for the rat small intestine. Br J Pharmacol 124(7):1385–1394PubMedCrossRef Bertrand V, Guimbaud R, Tulliez M, Mauprivez C, Sogni P, Couturier D et al (1998) Increase in tumor necrosis factor-alpha production linked to the toxicity of indomethacin for the rat small intestine. Br J Pharmacol 124(7):1385–1394PubMedCrossRef
10.
go back to reference Suenaert P, Bulteel V, Lemmens L, Noman M, Geypens B, Van Assche G et al (2002) Anti-tumor necrosis factor treatment restores the gut barrier in Crohn’s disease. Am J Gastroenterol 97(8):2000–2004PubMedCrossRef Suenaert P, Bulteel V, Lemmens L, Noman M, Geypens B, Van Assche G et al (2002) Anti-tumor necrosis factor treatment restores the gut barrier in Crohn’s disease. Am J Gastroenterol 97(8):2000–2004PubMedCrossRef
11.
go back to reference van Bergeijk JD, Wilson JH, Nielsen OH, von Tirpitz C, Karvonen AL, Lygren I et al (2002) Octreotide in patients with active ulcerative colitis treated with high dose corticosteroids (OPUS 1). Eur J Gastroenterol Hepatol 14(3):243–248PubMedCrossRef van Bergeijk JD, Wilson JH, Nielsen OH, von Tirpitz C, Karvonen AL, Lygren I et al (2002) Octreotide in patients with active ulcerative colitis treated with high dose corticosteroids (OPUS 1). Eur J Gastroenterol Hepatol 14(3):243–248PubMedCrossRef
12.
go back to reference Eliakim R, Karmeli F, Okon E, Rachmilewitz D (1993) Octreotide effectively decreases mucosal damage in experimental colitis. Gut 34(2):264–269PubMedCrossRef Eliakim R, Karmeli F, Okon E, Rachmilewitz D (1993) Octreotide effectively decreases mucosal damage in experimental colitis. Gut 34(2):264–269PubMedCrossRef
13.
go back to reference Kucharzik T, Lugering A, Lugering N, Rautenberg K, Linnepe M, Cichon C et al (2000) Characterization of M cell development during indomethacin-induced ileitis in rats. Aliment Pharmacol Ther 14(2):247–256PubMedCrossRef Kucharzik T, Lugering A, Lugering N, Rautenberg K, Linnepe M, Cichon C et al (2000) Characterization of M cell development during indomethacin-induced ileitis in rats. Aliment Pharmacol Ther 14(2):247–256PubMedCrossRef
14.
go back to reference Bernardes-Silva CF, Damiao AO, Sipahi AM, Laurindo FR, Iriya K, Lopasso FP et al (2004) Ursodeoxycholic acid ameliorates experimental ileitis counteracting intestinal barrier dysfunction and oxidative stress. Dig Dis Sci 49(10):1569–1574PubMedCrossRef Bernardes-Silva CF, Damiao AO, Sipahi AM, Laurindo FR, Iriya K, Lopasso FP et al (2004) Ursodeoxycholic acid ameliorates experimental ileitis counteracting intestinal barrier dysfunction and oxidative stress. Dig Dis Sci 49(10):1569–1574PubMedCrossRef
15.
go back to reference Goncalves J, Queiroz G (1996) Purinoceptor modulation of noradrenaline release in rat tail artery: tonic modulation mediated by inhibitory P2Y- and facilitatory A2A-purinoceptors. Br J Pharmacol 117(1):156–160PubMed Goncalves J, Queiroz G (1996) Purinoceptor modulation of noradrenaline release in rat tail artery: tonic modulation mediated by inhibitory P2Y- and facilitatory A2A-purinoceptors. Br J Pharmacol 117(1):156–160PubMed
16.
go back to reference Wyatt J, Vogelsang H, Hubl W, Waldhoer T, Lochs H (1993) Intestinal permeability and the prediction of relapse in Crohn’s disease. Lancet 341(8858):1437–1439PubMedCrossRef Wyatt J, Vogelsang H, Hubl W, Waldhoer T, Lochs H (1993) Intestinal permeability and the prediction of relapse in Crohn’s disease. Lancet 341(8858):1437–1439PubMedCrossRef
17.
go back to reference Garcia-Lafuente A, Antolin M, Guarner F, Crespo E, Malagelada JR (2001) Modulation of colonic barrier function by the composition of the commensal flora in the rat. Gut 48(4):503–507PubMedCrossRef Garcia-Lafuente A, Antolin M, Guarner F, Crespo E, Malagelada JR (2001) Modulation of colonic barrier function by the composition of the commensal flora in the rat. Gut 48(4):503–507PubMedCrossRef
18.
go back to reference Hogenauer C, Aichbichler B, Santa Ana C, Porter J, Fordtran J (2002) Effect of octreotide on fluid absorption and secretion by the normal human jejunum and ileum in vivo. Aliment Pharmacol Ther 16(4):769–777PubMedCrossRef Hogenauer C, Aichbichler B, Santa Ana C, Porter J, Fordtran J (2002) Effect of octreotide on fluid absorption and secretion by the normal human jejunum and ileum in vivo. Aliment Pharmacol Ther 16(4):769–777PubMedCrossRef
19.
go back to reference Lamrani A, Tulliez M, Chauvelot-Moachon L, Chaussade S, Mauprivez C, Hagnere AM et al (1999) Effects of octreotide treatment on early TNF-alpha production and localization in experimental chronic colitis. Aliment Pharmacol Ther 13(5):583–594PubMedCrossRef Lamrani A, Tulliez M, Chauvelot-Moachon L, Chaussade S, Mauprivez C, Hagnere AM et al (1999) Effects of octreotide treatment on early TNF-alpha production and localization in experimental chronic colitis. Aliment Pharmacol Ther 13(5):583–594PubMedCrossRef
20.
go back to reference Suenaert P, Bulteel V, Vermeire S, Noman M, Van Assche G, Rutgeerts P (2005) Hyperresponsiveness of the mucosal barrier in Crohn’s disease is not tumor necrosis factor-dependent. Inflamm Bowel Dis 11(7):667–673PubMedCrossRef Suenaert P, Bulteel V, Vermeire S, Noman M, Van Assche G, Rutgeerts P (2005) Hyperresponsiveness of the mucosal barrier in Crohn’s disease is not tumor necrosis factor-dependent. Inflamm Bowel Dis 11(7):667–673PubMedCrossRef
21.
go back to reference Colpaert S, Liu Z, De Greef B, Rutgeerts P, Ceuppens JL, Geboes K (2001) Effects of anti-tumour necrosis factor, interleukin-10 and antibiotic therapy in the indometacin-induced bowel inflammation rat model. Aliment Pharmacol Ther 15(11):1827–1836PubMedCrossRef Colpaert S, Liu Z, De Greef B, Rutgeerts P, Ceuppens JL, Geboes K (2001) Effects of anti-tumour necrosis factor, interleukin-10 and antibiotic therapy in the indometacin-induced bowel inflammation rat model. Aliment Pharmacol Ther 15(11):1827–1836PubMedCrossRef
Metadata
Title
Protective Effect of Octreotide and Infliximab in an Experimental Model of Indomethacin-Induced Inflammatory Bowel Disease
Authors
Dídia H. Bismara Cury
José Edson Costa
Kioshi Irika
Luciana Mijji
Alessandre Garcez
Carlos Buchiguel
Ivani Silva
Aytan Sipahi
Publication date
01-09-2008
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 9/2008
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-007-0172-z

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