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Effect of urinary trypsin inhibitor on pancreatic cellular and lysosomal fragility in cerulein-induced acute pancreatitis in rats

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Abstract

We evaluated the protective effect and the mechanism of action of the trypsin inhibitor, urinastatin, extracted from human urine, in experimental acute pancreatitis induced by a supramaximal dose of cerulein (5 μg/kg/hr for 3.5 hr). Urinastatin in a dose of 10,000 units/kg/hr was given by three different methods of continuous infusion: (1) 2 hr before and during cerulein infusion, (2) only during cerulein infusion, and (3) starting 1 hr after the beginning of cerulein infusion and continued for 3.5 hr. In protocol 1 and 2 urinastatin was significantly more protective than in 3. In protocol 1 urinastatin was very protective in all parameters tested (serum amylase level, pancreatic water and amylase content, distribution of lysosomal enzymes, cellular and lysosomal fragility). These results suggest that the administration of urinastatin before and during cerulein infusion may suppress the pathogenesis and evolution of pancreatitis by inhibiting the chain reaction of pancreatic enzyme activation closely related to redistribution of lysosomal enzyme and lysosomal fragility.

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References

  1. Koike H, Steer ML, Meldolesi J: Pancreatic effects of ethionine; blockage of exocytosis and appearance of crinophagy and autophagy precede cellular necrosis. Am J Physiol 242:G297–307, 1982

    Google Scholar 

  2. Watanabe O, Baccino FM, Steer ML, Meldolesi J: Supramaximal caerulein stimulation on the ultrastructure of rat pancreatic acinar cell: Early morphological changes during development of experimental pancreatitis. Am J Physiol 246:G457–467, 1984

    Google Scholar 

  3. Nidereau C, Ferrell LD, Grendell JH: Caerulein induced acute necrotizing pancreatitis in mice; protective effects of proglumide, benzotript, and secretin. Gastroenterology 88:1192–1204, 1985

    Google Scholar 

  4. Steer ML, Meldolesi J: The cell biology of experimental acute pancreatitis. N Engl J Med 316:144–150, 1987

    Google Scholar 

  5. Saluja A, Hashimoto S, Saluja M, Powers RE, Meldolesi J, Steer ML: Subcellular redistribution of lysosomal enzymes during caerulein-induced pancreatitis. Am J Physiol 253:G508–516, 1987

    Google Scholar 

  6. Saito I, Hashimoto S, Saluja A, Steer ML, Meldolesi J: Intracellular transport of pancreatic zymogens during caerulein supramaximal stimulation. Am J Physiol 253:G516–526, 1987

    Google Scholar 

  7. Ohshio G, Saluja A, Leli U, Sengputa A, Steer ML: Esterase inhibitor prevent lysosomal enzyme redistribution in two noninvasive models of experimental pancreatitis. Gastroenterology 96:853–859, 1989

    Google Scholar 

  8. Bauer J, Reich Z: Uber die antitryptishe Wirkung des Harns. Med Klin 46:1744–1747, 1969

    Google Scholar 

  9. Sumi H, Takada H, Takada A: Studies on human urinary trypsin inhibitor. 1. Its modification on treatment of urine with acid. Thromb Res 11:747–754, 1977

    Google Scholar 

  10. Faarvang HJ, Knudsen PJ: Hyaluronidase inhibitor and trypsin inhibitor in preparations from human urine. Proc Soc Exp Biol Med 108:591–592, 1961

    Google Scholar 

  11. Faarvang HJ: Urinary trypsin inhibitor in man. Scand J Clin Lab Invest 17:1–78, 1965

    Google Scholar 

  12. Bernfeld P: Amylase α and β. Methods Enzymol 1:149–158, 1955

    Google Scholar 

  13. McDonald JK, Ellis S: On the substrate specificity of cathepsin B1 and B2 including a new fluorogenic substrate for cathepsin B1. Life Sci 17:1269–1276, 1975

    Google Scholar 

  14. Labarca C, Paigen K: A simple, rapid and sensitive DNA assay procedure. Anal Biochem 102:334–352, 1980

    Google Scholar 

  15. Powers RE, Saluja AK, Houlihan MJ, Steer ML: Diminished agonist-stimulated inositol triphosphate generation block stimulus-secretion coupling in mouse pancreatic acini during diet-induced experimental pancreatitis. J Clin Invest 77:1668–1674, 1986

    Google Scholar 

  16. Bergmeyer HU, Bernt E, Hess B: Lactic dehydrogenase.In Methods in Enzymatic Analysis. HU Bergmeyer (ed). New York, Academic Press, 1963, pp 736–741

    Google Scholar 

  17. Greenbaum LM, Hirshkowitz A, Schoichet I: The activation of trypsinogen by cathepsin B. J Biol Chem 234:2885–2890, 1959

    Google Scholar 

  18. Greenbaum LM, Hirchkowitz A: Endogenous cathepsin B activation of trypsinogen in extracts of dog pancreas. Proc Soc Exp Biol Med 107:74–76, 1961

    Google Scholar 

  19. Rinderknecht H: Activation of pancreatic zymogens. Normal activation, premature intrapancreatic activation, protective mechanism against inappropriate activation. Dig Dis Sci 31:314–321, 1986

    Google Scholar 

  20. Figarrella C, Miszczuk-Jamska B, Barrett AJ: Possible lysosomal activation of pancreatic zymogens. Activation of both human trypsinogen by cathepsin B and spontaneous acid activation of human trypsinogen I. Biol Chem Hoppe-Seyler 369(suppl):293–295, 1988

    Google Scholar 

  21. Steer ML, Meldolesi J, Figarella C: Pancreatitis; the role of lysosomes. Dig Dis Sci 29:934–938, 1984

    Google Scholar 

  22. Shikimi T, Hanada M: Inhibitory effect of human urinary trypsin inhibitor (urinastatin) on lysosomal thiol proteinase. Jpn J Pharmacol 42:571–574, 1986

    Google Scholar 

  23. Oda T, Sameshima T, Miyatake T, Miyao J: Antishock effects of urinary trypsin inhibitor, MR-20 Anesthesia 33:137–142, 1984 (in Japanese)

    Google Scholar 

  24. Ohnishi H, Kosuzume H, Ashida Y, Kato K, Honjo I: Effects of urinary trypsin inhibitor on pancreatic enzymes and experimental acute pancreatitis. Dig Dis Sci 29:26–32, 1984

    Google Scholar 

  25. Tani S, Otsuki M, Itoh H, Nakamura T, Fujii M, Okabayashi Y, Fujisawa T, Baba S: The protective effect of the trypsin inhibitor urinastatin on caerulein-induced acute pancreatitis in rats. Pancreas 3:471–476, 1988

    Google Scholar 

  26. Saluja M, Saluja A, Zavertonik A, Hirano T, Steer ML: A plasma factor is involved in subcellular redistribution of lysosomal enzyme which follows supramaximal pancreatic stimulation with caerulein. Pancreas 4:640, 1989 (abstract)

    Google Scholar 

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Hirano, T., Manabe, T. & Tobe, T. Effect of urinary trypsin inhibitor on pancreatic cellular and lysosomal fragility in cerulein-induced acute pancreatitis in rats. Digest Dis Sci 38, 660–664 (1993). https://doi.org/10.1007/BF01316797

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