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Proteases and protease inhibitors in taurocholate-induced acute pancreatitis in rats

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Summary

Background. Proteases and protease inhibitors have been indicated to play an important role in both human and experimental acute pancreatitis, although little is known about them in rats.

Methods. Three percent sodium taurocholate was infused into the bilio-pancreatic duct to induce AP, and over 0–72 h we measured lipase, amylase, albumin, prekallikrein, factor X, α-1-macroglobulin, α-2-antiplasmin, antithrombin III, α-1-protease inhibitor, and C1-esterase inhibitor (all in plasma) and histologic and macroscopic findings.

Results. A severe necrotizing, nonlethal, AP was induced with an early increase in plasma lipase and α-amylase activity levels and peritoneal exudate followed by a return to near control levels after 72 h. Histologic score and pancreatic wet weight ratio increased initially and remained high during the observation period. The protease inhibitors C1-esterase inhibitor, α-2-antiplasmin, and antithrombin III decreased early, within 0–6 h, whereafter levels normalized. The protease inhibitors α-1-macroglobulin and α-1-protease inhibitor later gradually decreased over the 72 h.

Conclusion. Taurocholate-induced acute pancreatitis (AP) in the rat mimics early necrotizing human pancreatitis. Protease activation and protease inhibitor consumption occur consistent with a two-stage development, and contact-phase activation is a possible primary event in this model.

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References

  1. Büchler M, Beger HG. Standards in experimental acute pancreatitis. Scand J Gastroenterol 1992;24(Suppl 1):1–92.

    Google Scholar 

  2. Aho HJ, Koskensalo SM, Nevalainen TJ. Experimental pancreatitis in the rat. Sodium taurocholate-induced acute haemorrhagic pancreatitis. Scand J Gastroenterol 1980;15:411–416.

    Article  PubMed  CAS  Google Scholar 

  3. Armstrong CP, Taylor TV, Torrance HB. Pressure, volume and the pancreas. Gut 1985; 26: 615–624.

    Article  PubMed  CAS  Google Scholar 

  4. Lerch MM, Adler G. Experimental animal models of acute pancreatitis. Review. Int J Pancreatol 1994; 15: 159–170.

    PubMed  CAS  Google Scholar 

  5. Lankisch PG, Ihse I. Bile-induced acute experimental pancreatitis. Scand J Gastroenterol 1987; 22: 257–260.

    Article  PubMed  CAS  Google Scholar 

  6. Schmidt J, Rattner DW, Lewandrowski K, Compton CC, Mandavilli U, Knoefel WT, et al. A better model of acute pancreatitis for evaluating therapy. Ann Surg 1992; 215: 44–56.

    Article  PubMed  CAS  Google Scholar 

  7. Azima B, Kao RL, Youngberg G, Williams D, Browder W. A new animal model of reversible acute pancreatitis. J Surg Res 1996; 63: 419–424.

    Article  PubMed  CAS  Google Scholar 

  8. Kingsnorth A. Mediators in acute pancreatitis. Scand J Gastroenterol Suppl 1996; 31 (Suppl. 219): 1–50.

    Google Scholar 

  9. Lasson A, Ohlsson K. Acute pancreatitis. The correlation between clinical course, protease inhibitors, and complement and kinin activation. Scand J Gastroenterol 1984; 19: 707–710.

    PubMed  CAS  Google Scholar 

  10. Rao KN, Tuma J, Lombardi B. Acute hemorrhagic necrosis in mice. Intraparenchymal activation of zymogens, and other enzyme changes in pancreas and serum. Gastroenterology 1976; 70: 720–726.

    PubMed  CAS  Google Scholar 

  11. Ohlsson K, Olsson R, Bjork P, Balldin G, Borgstrom A, Lasson A, et al. Local administration of human pancreatic secretory trypsin inhibitor prevents the development of experimental acute pancreatitis in rats and dogs. Scand J Gastroenterol 1989; 24: 693–704.

    Article  PubMed  CAS  Google Scholar 

  12. Lium B, Ruud TE, Pillgram-Larsen J, Stadaas JO, Aasen AO. Sodium taurocholate-induced acute pancreatitis in pigs. Pathomorphological studies of the pancreas in untreated animals and animals pretreated with high doses of corticosteroids or protease inhibitors. Acta Pathol Microbiol Immunol Scand A 1987; 95: 377–382.

    PubMed  CAS  Google Scholar 

  13. Laurell CB. Electroimmunoassay. Scand J Clin Lab Invest 1972; 29 (Suppl 124): 21–37.

    Article  CAS  Google Scholar 

  14. Gallimore MJ, Friberger P. Chromogenic peptide substrate assay and their clinical applications. Blood Rev 1991; 5: 117–127.

    Article  PubMed  CAS  Google Scholar 

  15. Matsuzawa T, Nomura M, Unno T. Clinical pathology reference ranges of laboratory animals. J Vet Med Sci 1993; 55 (3): 351–362.

    PubMed  CAS  Google Scholar 

  16. Gauthier F, Genell S, Mouray H, Ohlsson K. The in vitro interactions of rat pancreatic elastase and normal inflammatory rat serum. Biochim Biophys Acta 1978; 526: 218–226.

    PubMed  CAS  Google Scholar 

  17. Koj A, Magielska-Zero D, Kurdowska A, Bereta J. Proteinase inhibitors as acute phase reactants: Regulation of synthesis and turnover. Adv Exp Med Biol 1988; 240: 171–181.

    PubMed  CAS  Google Scholar 

  18. Kumada T, Abiko Y. Physiological role of alpha 2-plasmin inhibitor in rats. Thromb Res 1984; 36(2): 153–163.

    Article  PubMed  CAS  Google Scholar 

  19. Karges HE, Funk KA, Ronneberger H. Activity of coagulation and fibrinolysis parameters in animals. Arzneim Forsch/Drug Res 1994; 44 (1): 793–797.

    CAS  Google Scholar 

  20. Deng X, Sun Z, Lasson Å, Wang X, Andersson R. Alterations in the functions of the reticuloendothelial and protease-antiprotease systems after intraperitoneal injections of Zymosan in rats. Eur J Surg 1998; 164: 605–615.

    Article  PubMed  CAS  Google Scholar 

  21. Spormann H, Sokolowski A, Letko G. Effect of temporary ischemia upon development and histological patterns of acute pancreatitis in the rat. Pathol Res Pract 1989; 184: 507–513.

    PubMed  CAS  Google Scholar 

  22. Siegel S, Castellan NJ. Nonparametric Statistics for the Behavioral Sciences. McGraw-Hill, New York, 1988.

    Google Scholar 

  23. Luthen R, Niederau C, Niederau M, Ferrell LD, Grendell JH. Influence of ductal pressure and infusates on activity and subcellular distribution of lysosomal enzymes in the rat pancreas see comments. Gastroenterology 1995; 109: 573–581.

    Article  PubMed  CAS  Google Scholar 

  24. Merriam LT, Wilcockson D, Samuel I, Joehl RJ. Ligation-induced acute pancreatitis increases pancreatic and circulating trypsinogen activation peptides. J Surg Res 1996; 60: 417–421.

    Article  PubMed  CAS  Google Scholar 

  25. Arendt T, Broschewitz U. Bile induced acute oedematous pancreatitis in rats: non-parallel changes in pancreatic morphology and amylase release in vitro. Gut 1994; 35: 1127–1131.

    Article  PubMed  CAS  Google Scholar 

  26. Nonaka A, Manabe T, Kyogoku T, Tamura K, Tobe T. Evidence for a role of free radicals by synthesized scavenger, 2-octadecylascorbic acid, in cerulein-induced mouse acute pancreatitis. Dig Dis Sci 1992; 37: 274–279.

    Article  PubMed  CAS  Google Scholar 

  27. Schmidt J, Lewandrowski K, Fernandez-del Castillo C, Mandavilli U, Compton CC, Warshaw AL, et al. Histopathologic correlates of serum amylase activity in acute experimental pancreatitis. Dig Dis Sci 1992; 37: 1426–1433.

    Article  PubMed  CAS  Google Scholar 

  28. Foulis AK. Pathology of acute pancreatitis; in Glazer G, Ranson JHC, eds. Acute Pancreatitis. Experimental and Clinical Aspects of Pathogenesis and Management. Bailière Tindall, London, 1988; pp. 194–206.

    Google Scholar 

  29. Wanke M. Experimental acute pancreatitis. Review. Curr Top Pathol 1970; 52: 64–142.

    PubMed  CAS  Google Scholar 

  30. Aho HJ, Nevalainen TJ. Experimental pancreatitis in the rat. Ultrastructure of sodium taurocholate-induced pancreatic lesions. Scand J Gastroenterol 1980; 15: 417–424.

    PubMed  CAS  Google Scholar 

  31. Cochrane CG, Griffin JH. The biochemistry and pathophysiology of the contact system of plasma. Adv Immunol 1982; 33: 241–306.

    Article  PubMed  CAS  Google Scholar 

  32. Wachtfogel YT, DeLa Cadena RA, Colman RW. Structual biology, cellular interactions and pathophysiology of the contact system. Thromb Res 1993; 72: 1–21.

    Article  PubMed  CAS  Google Scholar 

  33. Shimizu I, Wada S, Okahisa T, Kamamura M, Yano M, Kodaira T, et al. Radioimmunoreactive plasma bradykinin levels and histological changes during the course of cerulein-induced pancreatitis in rats. Pancreas 1993; 8: 220–225.

    Article  PubMed  CAS  Google Scholar 

  34. Seelig R, Seelig HP. The possible role of serum complement system in the formal pathogenesis of acute pancreatitisis. I. Immunopathogenetic pancreatitis—local Schwartzman-Sanarelli phenomenon—endotoxin induced pancreatitis. Acta Hepatogastroenterol (Stuttg) 1975; 22: 263–268.

    CAS  Google Scholar 

  35. Weiser MR, Gibbs SA, Moore FD Jr, Hechtman HB. Complement inhibition by soluble complement receptor type 1 fails to moderate cerulein-induced pancreatitis in the rat. Int J Pancreatol 1996; 19(2): 129–134.

    PubMed  CAS  Google Scholar 

  36. Bergsma J, Boelen KM, Duursma AM, Schutter WG, Bouma JMW, Gruber M. Complexes of rat alpha-1-macroglobulin and subtilisin are endocytosed by parenchymal liver cells. Biochem J 1985; 226: 75–84.

    PubMed  CAS  Google Scholar 

  37. Brower HS, Harpel PC. Proteolytic cleavage and inactivation of a-2-plasmin inhibitor and C1 inactivator by human polymorphonuclear leukocyte elastase. J Biol Chem 1982; 257: 9849–9854.

    PubMed  CAS  Google Scholar 

  38. Rydzewska G, Kosidlo S, Gabryelewicz A, Rydzewski A. Tissue plasminogen activator, plasminogen activator inhibitor, and other parameters of fibrinolysis in the early stages of taurocholate acute pancreatitis in rats. Int J Pancreatol 1992; 11: 161–168.

    PubMed  CAS  Google Scholar 

  39. Högstorp HJ, Jacobsson H, Carlin G. Effect of hepatectomy on the post-traumatic fibrinolysis inhibition and the primary fibrinolysis inhibitor in the rat. Thromb Res 1980; 18: 361–368.

    Article  PubMed  Google Scholar 

  40. Gabryelewicz A, Kosidlo S, Prokopowicz J, Podkowicz K. Does heparin modify protease-antiprotease balance in acute experimental pancreatitis in rats. Hepatogastroenterology 1986; 33: 79–82.

    PubMed  CAS  Google Scholar 

  41. Gauthier F, Genell S, Mouray H, Ohlsson K. Interactions in vitro and in vivo between rat serum protease inhibitors and anodal and cathodal rat trypsin and chymotrypsin. Biochim Biophys Acta 1979; 566: 200–210.

    PubMed  CAS  Google Scholar 

  42. Foitzik T, Lewandrowski KB, Fernandez-del Castillo C, Rattner DW, Warshaw AL. Evidence for extraluminal trypsinogen activation in three different models of acute pancreatitis. Surgery 1994; 115: 698–702.

    PubMed  CAS  Google Scholar 

  43. Lungarella G, Gardi C, de Santi MM, Luzi P. Pulmonary vascular injury in pancreatitis: evidence for a major role played by pancreatic elastase. Exp Mol Pathol 1985; 42: 44–59.

    Article  PubMed  CAS  Google Scholar 

  44. Tsuji A, Akamatsu T, Nagamune H, Matsuda Y. Identification of targeting proteinase for rat alpha-1-macroglobulin. Biochem J 1994; 298: 79–85.

    PubMed  CAS  Google Scholar 

  45. Largman C, Reidelberger RD, Tsukamoto H. Correlation of trypsin-plasma inhibitor complexes with mortality in experimental pancreatitis in rats. Dig Dis Sci 1986; 31: 961–969.

    Article  PubMed  CAS  Google Scholar 

  46. Schmidt J, Fernandez-del Castillo C, Rattner DW, Lewandrowski K, Compton CC, Warshaw AL. Trypsinogen-activation peptides in experimental rat pancreatitis: prognostic implications and histopathologic correlates. Gastroenterology 1992; 103: 1009–1016.

    PubMed  CAS  Google Scholar 

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Kruse, P., Hage, E. & Lasson, Å. Proteases and protease inhibitors in taurocholate-induced acute pancreatitis in rats. International Journal of Pancreatology 25, 113–121 (1999). https://doi.org/10.1385/IJGC:25:2:113

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  • DOI: https://doi.org/10.1385/IJGC:25:2:113

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