Skip to main content

Advertisement

SpringerLink
Log in

Increased permeability occurs in rat ileum following induction of pancolitis

  • Gastrointestinal Oncology
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Acetic acid-induced pan colitis in rats leads not only to colonic injury but also to a bystander ileal injury, characterized by decreased fluid and electrolyte absorption without associated histological injury or infiltration of inflammatory cells. To examine the nature of this decreased ileal fluid and electrolyte absorption, we measured effect of acetic acid-induced pancolitis on ileal transmural sodium and chloride transport, as well as on ileal permeability to mannitol and inulin on mucosal sheets mounted in Ussing chambers. In addition, ileal tight junctional morphology was assessed by electron microscopy. In colitic animals, ileal serosal-to-mucosal sodium and chloride transmural fluxes were increased (P<0.05); compatible with the observed decrease in net fluid absorption. Mannitol and inulin ileal serosal-to-mucosal and mucosal-to-serosal ileal fluxes were similarly increased (P<0.05), suggesting that an increase in ileal permeability occurred during acetic acid-induced pancolitis. This increase in ileal permeability was not accompanied by changes in tight junctional ultrastructure. These results suggest that: (1) the decrease in ileal fluid and electrolyte absorption seen during acetic acid-induced rat pancolitis occurred in parallel with a rise in both transcellular and paracellular permeability, and (2) the ileal permeability changes were not accompanied by structural changes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Sanderson IR, Boulton P, Menzies IS, Walker-Smith JA: Improvement of abnormal lactulose/rhamnose permeability in active Crohn's disease of the small bowel by an elemental diet. Gut 28:1073–1076, 1987

    PubMed  Google Scholar 

  2. Bjarnason I, Zanelli G, Smith T, Prouse P, Williams P, Smethurst P, Delacey G, Gumpel MJ, Levi AJ: Nonsteroidal antiinflammatory drug-induced intestinal inflammation in humans. Gastroenterology 93:480–489, 1987

    PubMed  Google Scholar 

  3. Hamilton I, Cobden I, Rothwell J, Axon ATR: Intestinal permeability in coeliac disease: The response to gluten withdrawal and singe-dose gluten challenge. Gut 23:202–210, 1982

    PubMed  Google Scholar 

  4. Madara JL, Stafford J: Interferon-gamma directly affects barrier function of cultured intestinal epithelial monolayer. J Clin Invest 83:724–727, 1989

    PubMed  Google Scholar 

  5. Krugkliak P, Hollander D, Le K, Ma T, Dadufalza VD, Katz KD: Regulation of polyethylene glycol 400 intestinal permeability by endogenous and exogenous prostanoids. Influence of non-steroidal anti-inflammatory drugs. Gut 31:417–421, 1990

    PubMed  Google Scholar 

  6. Wellmann W, 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

    PubMed  Google Scholar 

  7. Empey LR, Cui N, Fedorak RN: Acetic acid-induced colitis results in bystander ileal injury. Agents Actions 38:76–84, 1993

    PubMed  Google Scholar 

  8. Pantzar N, Ekstrom GM, Wang Q, Westrom BR: Mechanisms of increased intestinal [51Cr]EDTA absorption during experimental colitis in the rat. Dig Dis Sci 39:2327–2333, 1994

    PubMed  Google Scholar 

  9. McLeod AD, Fedorak RN, Friend DR, Tozer TN, Cui N: A glucocorticoid prodrug facilitates normal mucosal function in rat colitis without adrenal suppression. Gastroenterology 106:405–413, 1994

    PubMed  Google Scholar 

  10. Fedorak RN, Empey LR, MacArthur C, Jewell LD: Misoprostol provides a colonic mucosal protective effect during acetic acid-induced colitis in rats. Gastroenterology 98:615–625, 1990

    PubMed  Google Scholar 

  11. Charney AN, Goldfarb AS, Egnor RW: Effects of pH and cyclic adenosine monophosphate on ileal electrolyte transport in the rat and rabbit. Gastroenterology 100:410–418, 1991

    PubMed  Google Scholar 

  12. O'Loughlin EV, Gall DG: Small intestinal absorption and secretion of fluid and electrolytes.In Gastrointestinal Secretion. JS Davison (ed). London, Wright, 1989, pp 157–170

    Google Scholar 

  13. Moore R, Pothoulakis C, LaMont JT, Carlson S, Madara JL:C. difficile toxin A increases intestinal permeability and induces Cl− secretion. Am J Physiol 259(2 pt 1):G165-G172, 1990

    PubMed  Google Scholar 

  14. Hollander D: The intestinal permeability barrier. Scand J Gastroenterol 27:721–726, 1992

    PubMed  Google Scholar 

  15. Hollander D: Crohn's disease—a permeability disorder of the tight junction? Gut 29:1621–1624, 1988

    PubMed  Google Scholar 

  16. Jodal M, Fihn BM, Sjoqvist A: Effect of glucose on passive transport of extracellular probes across the rat small intestinal epitheliumin vivo. Gastroenterology 106:241, 1994

    Google Scholar 

  17. Atisook K, Carlson S, Madara JL: Effects of phlorizin and sodium on glucose-elicited alterations of cell junctions in intestinal epithelia. J Am Physiol 258 (1 pt 1):C77-C85, 1990

    Google Scholar 

  18. Flick JA, Tai YH, Levine SL, Watson AM, Montrose JM, Madara JL, Donowitz M: Intracellular Ca2+ regulation of tight junction resistance in T84 monolayer-a protein kinase C effect. Gastroenterology 100:A686, 1991

    Google Scholar 

  19. Phillips TE, Phillips TL, Neutra MR: Macromolecules can pass through occluding junctions of rat ileal epithelium during cholinergic stimulation. Cell Tissue Res 247:547–554, 1987

    PubMed  Google Scholar 

  20. Madara JL, Barenberg D, Carlson S: Effects of cytochalasin D on occluding junctions of intestinal absorptive cells: Further evidence that the cytoskeleton may influence paracellular permeability and junctional charge selectivity. J Cell Biol 102:2125–2136, 1986

    PubMed  Google Scholar 

  21. Schulzke J, Fromm M, Bentzel CJ, Zeitz M, Menge H, Reicken E: Ion transport in the experimental short bowel syndrome of the rat. Gastroenterology 102:479–504, 1992

    Google Scholar 

  22. Weiss SJ: Tissue destruction by neutrophils. N Engl J Med 320:365–376, 1989

    PubMed  Google Scholar 

  23. Nash S, Stafford J, Madara JL: Effects of polymorphonuclear leukocyte transmigration on the barrier function of cultured intestinal epithelial monolayers. J Clin Invest 80:1104–1113, 1987

    PubMed  Google Scholar 

  24. Von Ritter C, Grisham MB, Hollwarth M, Inauen W, Granger DN: Neutrophil-derived oxidants mediate formyl-methionylleucyl-phenylalanine-induced increases in mucosal permeability in rats. Gastroenterology 97:778–780, 1989

    PubMed  Google Scholar 

  25. Hollander D, Vadheim CM, Brettholz E, Petersen GM, Delahunty T, Rotter JI: Increased intestinal permeability in patients with Crohn's disease and their relatives. Ann Intern Med 105:883–885, 1986

    PubMed  Google Scholar 

  26. Sartor RB, Bond TM, Schwab JH: Systemic uptake and intestinal inflammatory effects of luminal bacterial cell wall polymers in rat with acute colonic injury. Infect Immun 56:2101–2108, 1988

    PubMed  Google Scholar 

  27. Hobson CH, Butt TJ, Ferry DM, Hunter J, Chadwick VS, Broom MF: Enterohepatic circulation of bacterial chemotactic peptide in rats with experimental colitis. Gastroenterology 94:1006–1013, 1988

    PubMed  Google Scholar 

  28. Cui N, Friend DR, Fedorak RN: A budesonide prodrug accelerates treatment of colitis in rats. Gut 35:1439–1446, 1994

    PubMed  Google Scholar 

  29. Jacobson K, McHugh K, Collins SM: Distal colitis causes changes in enteric nerve function at distant non-inflamed sites in the gut. Gastroenterology 104 (part 2):A717, 1993

    Google Scholar 

  30. Gross V, Andus T, Caesar I, Roth M, Scholmerich J: Evidence for continuous stimulation of interleukin-6 production in Crohn's disease. Gastroenterology 103:1120–1121, 1990

    Google Scholar 

  31. Alstead EM, McConnell JS, Exley AR, Hodgson HJF, Cohen J: Relationship between endotoxin, tumour necrosis factor-α and disease activity in inflammatory bowel disease. Eur J Gastroenterol Hepatol 3:325–328, 1991

    Google Scholar 

  32. Andus T, Gross V, Casar I, Krumm D, Hosp J, David M, Scholmerich J: Activation of monocytes during inflammatory bowel disease. Pathobiology 59:166–170, 1991

    PubMed  Google Scholar 

  33. McKay DM, Croitoru K, Brattsand R, and Perdue MH: TNFα causes epithelial (T84) permeability and secretory abnormalities in a co-culture model of inflammation. Gastroenterology 106:A732, 1994

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. From the Division of Gastroenterology, Department of Medicine; Department of Anatomy and Cell Biology, University of Alberta, Edmonton, Alberta, Canada

    Ningren Cui MD, Karen L. Madsen PhD, David R. Friend PhD, Bruce R. Stevenson PhD &  Richard N. Fedorak MD

  2. Stanford Research Institute, Menlo Park, California, USA

    Ningren Cui MD, Karen L. Madsen PhD, David R. Friend PhD, Bruce R. Stevenson PhD &  Richard N. Fedorak MD

Authors
  1. Ningren Cui MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Karen L. Madsen PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David R. Friend PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bruce R. Stevenson PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Richard N. Fedorak MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cui, N., Madsen, K.L., Friend, D.R. et al. Increased permeability occurs in rat ileum following induction of pancolitis. Digest Dis Sci 41, 405–411 (1996). https://doi.org/10.1007/BF02093836

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02093836

Key words

Search

Navigation