Skip to main content
Log in

Experimental Model of Acute Pancreatitis in Wistar Rat: Glucocorticoid Treatment Profile

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

Abstract

Severe acute pancreatitis may be triggered by an extrapancreatic insult at the peri-Vaterian duodenum such as that occurring in the short-term, 20 min closed duodenal loop model in Wistar rat, which mimics biliary acute pancreatitis or that following endoscopy. Glucocorticoids are immunological modulators whose therapeutic value is worth investigating. Wistar male rats were used under standardized conditions. Acute pancreatitis was induced by instillation of a 7% sodium tauraocholate solution with 5 drops of methylene blue to monitor absence of duodenal bilio pancreatic reflux into the peri-Vaterian duodenum for 20 min. Detection of biliopancreatic reflux with methylene blue was an exclusion criterion. Different doses and times of administration of subcutaneous hydrocortisone were evaluated. Biochemical assays were carried out in blood samples and pancreatic and lung tissue, while histpathological studies were done in the pancreas, lung liver, duodenum, spleen, kidneys, suprarenal glands, and stomach. Animals subjected to the experimental model developed severe acute pancreatitis. According to the dose and time ofadministration, hydrocortisone therapy was effective and beneficial at a dose of 4 mg/kg give 30 min before inducing acute pancreatitis. It was ineffective when doses were <4 mg/kg and given before sodium taurocholate harmful when the dose was >4 mg/kg and given either before or after. Thus, the proposed model is valid and useful to study the initiation mechanism of acute pancreatitis caused extrapancreatically while its amelioration by glucocorticoid is related the dose and time factor to achieve therapeutical results.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

REFERENCES

  1. Uhl W, Isenmann R, Curti G: Influence of etiology on the course and outcome of acute pancreatitis. Pancreas 13:335–343, 1996

    Google Scholar 

  2. Delcenserie R, Yzet T: Pancréatite aiguë: physiopathogénie, application au traitement médical. Hepatogastroenterolgy 6:16–21, 1999

    Google Scholar 

  3. Wilson C, Imrie C, Carter D: Fatal acute pancreatitis. Gut 29:782–788, 1998

    Google Scholar 

  4. Banks, P: Acute pancreatitis: clinical presentation. In V. Go, J. Gardener, F. Brooks, E. Lebenthal, E. Di Magno, G. Scheele, (eds) The exocrine pancreas: biology, pathobiology and disease, 2nd ed. New York, Raven Press, 1993, pp 475–480

    Google Scholar 

  5. Bhatia M, Saluja A, Steer M: The effects of neutrophil depletion on a completely non-invasive model of acute pancreatitis associated lung injury. Int J Pancreatol 24:77–83, 1998

    Google Scholar 

  6. McFadden D: Organ failure and multiple organ system failure in pancreatitis. Pancreas 6:S37–S43, 1991

    Google Scholar 

  7. Dagorn J: Physiopathologie de l'inflammation pancréatique au cours de la pancréatite aiguë. Hepatogastroenterology, Interalogy 6:9–15, 1999

    Google Scholar 

  8. Rinderknecht H: Fatal pancreatitis: a consequence of excessive leukocyte stimulation? Int J. Pancreatol 33:102–112, 1988

    Google Scholar 

  9. Simms H, D'Amico R: Polymorphonuclear leukocyte dysregulation during the systemic inflammatory response syndrome. Blood83:1398–1407, 1994

    Google Scholar 

  10. Ammori B, Leeder P, King R: Early increase in intestinal permeability in patients with severe acute pancreatitis: correlation with endotoxemia, organ failure and mortality. J Gastrointest Surg 3:252–262, 1999

    Google Scholar 

  11. Lerch M, Hernandez C, Adler G: Acute pancreatitis. N Engl J Med331:948–949, 1994

    Google Scholar 

  12. McKay C, Gallagher G, Brooks B: Increased monocyte cytokine production in association with systemic complications in acute pancreatitis.Br J Surg 83:919–923, 1996

    Google Scholar 

  13. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275, 1951

    Google Scholar 

  14. Negri G, Cosen-Binker LI, Bustos D: Myeloperoxidase (MPO) activity: a correlation with the inflammation degree in an experimental model of acute pancreatitis in the rat: Clin Chem Lab Med 39, (special suppl):S248, 2001

    Google Scholar 

  15. Técnicas Hematológicas Básicas I. In J. Davice, S. Lewis, J. Trigener Boixeda (eds). Hematologia, 2nd ed. Barcelona, Ediciones Toray, 1970, pp 19–50

    Google Scholar 

  16. Winer B, Brown D, Michels K: Statistical principles in experimental design. New York, McGraw-Hill, 1991

    Google Scholar 

  17. Iovanna J, Keim V, Dagorn J: Serum levels of pancreatitis-associated proteins indicators of the course of acute pancreatitis. Gastroenterology106:728–734, 1994

    Google Scholar 

  18. Friedler F, Iovanna J, Dagorn J: Acute-phase response of the rat pancreas protects against further aggression with severe necrotizing pancreatitis. Crit Care Med 26:887–894, 1998

    Google Scholar 

  19. Sherman S, Lehman G: A ERCP and endoscopic sphincterotomy-induced pancreatitis. Pancreas 6:350–357, 1991

    Google Scholar 

  20. Oezcueruemez-Porsch M, Kunz D, Hardt PD: Diagnostic relevance on interleukin pattern and acute-phase proteins in early phase of post-ERCP pancreatitis. Dig Dis Sci 43:1763–1769, 1998

    Google Scholar 

  21. Bordmerkel G, Kaw M, Balu R: Serum IL-6 levels in ERCP-induced pancreatitis. Pancreas 11:A423, 1995

    Google Scholar 

  22. Beauchant M, Barthet M: Peuton prévenir la pancréatite aiguë après cathétérisme endoscopique bilio-pancréatique? Hepatogastroenterology 8:7–9, 2001

    Google Scholar 

  23. Chen Y, Abdulian J, Collen M: Clinical outcome of post-ERCP pancreatitis. Relationship to history of previous pancreatitis. Am J Gastroenterol 90:2120–2123, 1995

    Google Scholar 

  24. Van Os E, Petersen B: Pancreatitis secondary to percutaneous liver biopsy-associated hemobilia. Am J Gastroenterol 91:557–580, 1996

    Google Scholar 

  25. Tiscornia O, Hamamura S, Lehmann E: Biliary acute pancreatitis: a review. World J Gastroenterol 6(2):157–168, 2000

    Google Scholar 

  26. Adler G, Nelson D, Katschinski M, Beglinger C: Neurohormonal control of human pancreatic exocrine secretion. Pancreas 10:1–13,1995

    Google Scholar 

  27. Jones B, Gores G: Physiology and pathophysiology of apoptosis in epithelial cells of the liver, pancreas and intestine. Am. J. Physiol. 273: G1174–G1188, 1997

    Google Scholar 

  28. Frossard J, Saluja A, Lee H: The role of intercellular adhesion molecule 1 and neutrophils in acute pancreatitis and pancreatitis-associated lung injury. Gastroenterology 116:694–701, 1999

    Google Scholar 

  29. Sandoval D, Gukovskaya A, Reavey P: The role of neutrophils and platelet-activating factor in mediating experimental pancreatitis. Gastroenterology 111:1081–1091, 1996

    Google Scholar 

  30. Abe R, Shimosigawa T, Toyota T: The role of endogenous glucocorticoids in rat experimental models of acute pancreatitis. Gastroen-terology109:933–943, 1995

    Google Scholar 

  31. Rangione A, Kusske A, Kwan K: IL-10 reduces the severity of acute pancreatitis in rats. Gastroenterology 112:960–967, 1997

    Google Scholar 

  32. Van Laethem J, Marchant A, Delvaux A: IL-10 prevents necrosis in murine experimental acute pancreatitis. Gastroenterology 108:1917–1922, 1995

    Google Scholar 

  33. Shäfer C, Williams J: Stress kinases and heat shock proteins in the pancreas: possible roles in normal function and disease. J Gastroenterol 35:1–9, 2000

    Google Scholar 

  34. Sternberg E: Neural-immune interaction in health and disease. J Clin Invest 100:2641–2647, 1997

    Google Scholar 

  35. Yamaguchi H, Weidenbach H, Adler G: Combined treatment with C1 esterase inhibitor and antithrombin improves survival in severe acute experimental pancreatitis. Gut 40:531–535, 1997

    Google Scholar 

  36. Norman J, Franz M, Messina J: Il-1 receptor antagonist decreases severity of experimental acute pancreatitis. Surgery 117:648–655, 1995

    Google Scholar 

  37. Kornberg R: Eukaryotic transcriptional control. Millenium Issue TCB 9:1679–1687, 1999

    Google Scholar 

  38. Blinman T, Gukovsky I, Gukovskaya S: Pancreatic acinar cells express a variety of cytokines that are regulated in experimental pancreatitis.Gastroenterology 112:A429, 1997

    Google Scholar 

  39. Kusske A, Rongione A, Reber H: Cytokines and acute pancreatitis.Gastroenterology 110:639–642, 1996

    Google Scholar 

  40. Jones B, Gores G: Physiology and pathophysiology of apoptosis in epithelial cells of the liver, pancreas and intestine. Am J Physiol 273: G1174–G1188, 1997

    Google Scholar 

  41. Santoro M: Regulation of the stress response by heat shock factors.Biochem Pharmacol. 59:1–63, 2000

    Google Scholar 

  42. Ponta H, Cato B, Herrlick P: Interference of specific transcription factors. Biochim Biophys Acta 1129:255–261, 1992

    Google Scholar 

  43. Herrlich P: Cross-talk between glucocorticoid receptor and AP-1. Oncogene 20:2465–2475, 2001

    Google Scholar 

  44. Scheinman K, Gualberto C, Jewell J: Characterization of the mechanism involved in the transrepression of Nf-·B by activated glucocorticoid receptors. Mol Cell Biol 15:943–953, 1996

    Google Scholar 

  45. Sheinman R, Cogswell P, Lofquist A, Baldwin A: Role of transcrpitional activation of I-·B in mediation of immunosuppression by glucocorticoids. Science 270:283–286, 1995

    Google Scholar 

  46. Caldenhoven E, Liden S, Wissinik A: Negative cross-talk between Rel A and the glucocorticoid receptor: a possible mechanism for the anti-inflammatory action of glucocorticoids. Mol. Endocrinol. 9:401–412, 1995

    Google Scholar 

  47. Auphan N, Di Donato J, Rosetti C: Immunosuppression by glucocorticoids: inhibition of Nf-·B activity through Induction of I kappa B synthesis. Science 270:286–290,1995

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cosen-Binker, L.I., Binker, M.G., Negri, G. et al. Experimental Model of Acute Pancreatitis in Wistar Rat: Glucocorticoid Treatment Profile. Dig Dis Sci 48, 1453–1464 (2003). https://doi.org/10.1023/A:1024791101859

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1024791101859

Navigation