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Experimental colitis in rats induces low-grade endotoxinemia without hepatobiliary abnormalities

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Abstract

In three experimental models in rats, surgical construction of a self-filling blind loop (SFBL), trinitrobenzene sulfonic acid (TNB) -induced colitis, and the combination of SFBL and TNB, the hypothesis was studied that intestine-derived endotoxins play a role in the pathogenesis of hepatobiliary disorders in chronic inflammatory bowel disease (CIBD). After eight weeks of treatment, a mild increase in portal and systemic endotoxin levels and interleukin-6 concentrations was observed and the serum levels of alkaline phosphatase, bilirubin, and ALAT were only mildly increased in SFBL plus TNB rats. Histopathological examination of the liver showed hardly any abnormalities in all three rat models. These results show that low-grade portal and systemic endotoxinemia in rats, induced by bacterial overgrowth and/or chemical colitis, is not able to induce hepatobiliary alterations. To exclude definitively a possible role for portal endotoxinemia in the pathogenesis of CIBD-associated hepatobiliary abnormalities, however, an adequate animal model for CIBD is urgently needed.

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References

  1. Desmet VJ, Geboes K: Liver lesions in inflammatory bowel disorders. J Pathol 151:247–255, 1987

    Google Scholar 

  2. Williams SM, Harned RK: Hepatobiliary complications of inflammatory bowel disease. Radiol Clin North Am 25:175–188, 1987

    Google Scholar 

  3. Ludwig J, LaRusso NF, Wiesner RH: The syndrome of primary sclerosing cholangitis.In Progress in Liver Diseases IX. H Popper, F Schaffner (eds). Philadelphia, WB Saunders, 1990, pp 555–566

    Google Scholar 

  4. Chapman RW: Primary sclerosing cholangitis. Clinical presentation, pathogenesis and treatment.In Autoimmune Liver Diseases. EL Krawitt, RH Wiesner (eds). New York, Raven Press, 1991, pp 191–203

    Google Scholar 

  5. Perrett AD, Higgins G, Johnston HH, Massarella GR, Truelove SC, Wright R: The liver in ulcerative colitis. QJ Med 40:211–238, 1971

    Google Scholar 

  6. Schrumpf E, Elgjo K, Fausa O, Gjone E, Kolmannskog F, Ritland S: Sclerosing cholangitis in ulcerative colitis. Scand J Gastroenterol 15:689–697, 1980

    Google Scholar 

  7. Lillemoe KD, Pitt HA, Cameron JL: Primary sclerosing cholangitis. Surg Clin North Am 70:1381–1402, 1990

    Google Scholar 

  8. Lindor KD, Wiesner RH, MacCarty RL, Ludwig J, LaRusso NF: Advances in primary sclerosing cholangitis. JAMA 89:73–80, 1990

    Google Scholar 

  9. Fausa O, Schrumpf E, Elgjo K: Relationship of inflammatory bowel disease and primary sclerosing cholangitis. Semin Liver Dis 11:31–39, 1991

    Google Scholar 

  10. Olaison G, Sjodahl R, Tagesson C: Abnormal intestinal permeability in Crohn's disease. A possible pathogenic factor. Scand J Gastroenterol 25:321–328, 1990

    Google Scholar 

  11. Teahon K, Smethurst P, Pearson M, Levi AJ, Bjarnason I: The effect of elemental diet on intestinal permeability and inflammation in Crohn's disease. Gastroenterology 101:84–89, 1991

    Google Scholar 

  12. Sherlock S: Pathogenesis of sclerosing cholangitis, the role of non-immune factors. Semin Liver Dis 11:5–10, 1991

    Google Scholar 

  13. Cameron DG, Watson GM, Witts LJ: The experimental production of macrocytic anaemia by operations on the intestinal tract. Blood 4:803–815, 1949

    Google Scholar 

  14. Lichtman SN, Keku J, Clark RL, Schwab JH, Sartor RB: Biliary tract disease in rats with experimental small bowel bacterial overgrowth. Hepatology 13:766–772, 1990

    Google Scholar 

  15. Lichtman SN, Sartor RB, Keku J, Schwab JH: Hepatic inflammation in rats with experimental small intestinal overgrowth. Gastroenterology 98:414–423, 1990

    Google Scholar 

  16. Morris GP, Beck PL, Herridge MS, Depew WT, Szewczuk MR, Wallace JL: Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology 96:795–803, 1989

    Google Scholar 

  17. Rachmilewitz D, Simon PL, Schwartz LW, Griswold DE, Fondacaro JD, Wasserman MA: Inflammatory mediators of experimental colitis in rats. Gastroenterology 97:326–337, 1989

    Google Scholar 

  18. Yamada T, Marshall S, Specian RD, Grisham MB: A comparative analysis of two models of colitis in rats. Gastroenterology 102:1524–1534, 1992

    Google Scholar 

  19. King CE, Toskes PP: The experimental rat blind loop preparation, a model for small-intestine bacterial overgrowth in man.In Animal Models for Intestinal Disease. CJ Pfeiffer (ed). Boca Raton, Florida, CRC Press, 1985, pp 217–223

    Google Scholar 

  20. Friberger P, Sörskog L, Nilsson K, Knös M: The use of a quantitative assay in endotoxin testing. Prog Clin Biol Res 231:149–169, 1987

    Google Scholar 

  21. Helle M, Boeije L, Aarden LA: Functional discrimination between interleukin 6 and interleukin 1. Eur J Immunol 18:1535–1540, 1988

    Google Scholar 

  22. Van Gool J, Boers W, de Nie I: Inhibitory effects of α2-macrofetoprotein (αm-FP) an acute phase globulin, on galactosamine hepatitis. Exp Mol Pathol 29:228–240, 1978

    Google Scholar 

  23. Smit JJH, Bosman DK, Jörning GGA, de Haan JG, Maas MAW, Chamuleau RAFM: The relationship between plasma free fatty acids and experimentally induced hepatic encephalopathy in the rat. Clin Chim Acta 197:95–104, 1991

    Google Scholar 

  24. Welkos SL, Toskes PP, Baer H, Smith GW: Importance of anaerobic bacteria in the cobalamin malabsorption of the experimental rat blind loop syndrome. Gastroenterology 80:313–320, 1981

    Google Scholar 

  25. Lichtman SN, Keku J, Schwab JH, Sartor RB: Hepatic injury associated with small bowel bacterial overgrowth in rats is prevented by metronidazole and tetracycline. Gastroenterology 100:513–519, 1991

    Google Scholar 

  26. Lichtman SN, Keku J, Schwab JH, Sartor RB: Evidence for peptidoglycan absorption in rats with experimental small bowel bacterial overgrowth. Infect Immun 59:555–562, 1991

    Google Scholar 

  27. Hartley MG, Hudson MJ, Swarbrick ET, Hill MJ, Gent AE, Helliers MD, Grace RH: The rectal mucosa-associated microflora in patients with ulcerative colitis. J Med Microbiol 36:96–103, 1992

    Google Scholar 

  28. Giaffer MH, Holdsworth CD, Duerden BI: The assessment of faecal flora in patients with inflammatory bowel disease by a simplified bacteriological technique. J Med Microbiol 35:238–243, 1991

    Google Scholar 

  29. Fox ES, Thomas P, Broitman SA: Hepatic mechanisms for clearance and detoxification of bacterial endotoxins. J Nutr Biochem 1:620–628, 1990

    Google Scholar 

  30. Wellmann P, Fink PC, Benner F, Schmidt FW: Endotoxemia in active Crohn's disease. Treatment with whole gut irrigation and 5-aminosalicylic acid. Gut 27:814–820, 1986

    Google Scholar 

  31. Heinrich PC, Castell JV, Andus T: Interleukin-6 and the acute phase response. Biochem J 265:621–636, 1990

    Google Scholar 

  32. Mahida YR, Kurlac L, Gallagher A, Hawkey CJ: High circulating concentrations of interleukin-6 in active Crohn's disease but not ulcerative colitis. Gut 32:1531–1534, 1991

    Google Scholar 

  33. Gross V, Andus T, Caesar I, Roth M, Scholmerich J: Evidence for continuous stimulation of interleukin-6 production in Crohn's disease. Gastroenterology 102:514–519, 1992

    Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, Medical Microbiology Academic Medical Center, Amsterdam, Z.O., The Netherlands

    H. S. Brand PhD, M.A.w. MAAS, A. Bosma MD, PhD, R. J. Van Ketel MD, PhD, P. Speelman MD, PhD & R. A. F. M. Chamuleau MD, PhD

  2. J. van Gool Laboratory for Experimental Internal Medicine, Academic Medical Center G2-136, Meibergdreef 9, 1105 AZ, Amsterdam, Z.O., The Netherlands

    H. S. Brand PhD, M.A.w. MAAS, A. Bosma MD, PhD, R. J. Van Ketel MD, PhD, P. Speelman MD, PhD & R. A. F. M. Chamuleau MD, PhD

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  1. H. S. Brand PhD, M.A.w. MAAS
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  2. A. Bosma MD, PhD
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  3. R. J. Van Ketel MD, PhD
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  4. P. Speelman MD, PhD
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  5. R. A. F. M. Chamuleau MD, PhD
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Brand, H.S., Bosma, A., Van Ketel, R.J. et al. Experimental colitis in rats induces low-grade endotoxinemia without hepatobiliary abnormalities. Digest Dis Sci 39, 1210–1215 (1994). https://doi.org/10.1007/BF02093785

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  • DOI: https://doi.org/10.1007/BF02093785

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