Experimental models of acute pancreatitis

COMMENTARY ON THE LAW

Experimental models of acute pancreatitis

Piotr Ceranowicz 1 , Jakub Cieszkowski 1 , Zygmunt Warzecha 1 , Artur Dembiński 1

1. Zakład Fizjologii Klinicznej, Katedra Fizjologii, Uniwersytet Jagielloński, Collegium Medicum

Published: 2015-02-21
DOI: 10.5604/17322693.1141101
GICID: 01.3001.0009.6499
Available language versions: en pl
Issue: Postepy Hig Med Dosw 2015; 69 : 264-269

 

Abstract

Acute pancreatitis is a severe disease with high mortality. Clinical studies can bring some data about etiology, pathogenesis and the course of acute pancreatitis. However, studies concerning early events of this disease and the new concepts of treatment cannot be performed on humans, due to ethical reasons. Animal models of acute pancreatitis have been developed to solve this problem. This review presents currently used experimental models of acute pancreatitis, their properties and clinical relevance. Experimental models of acute pancreatitis can be divided into in vivo (non-invasive and invasive) and ex vivo models. The onset, development, severity and extent of acute pancreatitis, as well as the mortality, vary considerably between these different models. Animal models reproducibly produce mild, moderate or severe acute pancreatitis. One of the most commonly used models of acute pancreatitis is created by administration of supramaximal doses of cerulein, an analog of cholecystokinin. This model produces acute mild edematous pancreatitis in rats, whereas administration of cerulein in mice leads to the development of acute necrotizing pancreatitis. Acute pancreatitis evoked by retrograde administration of sodium taurocholate into the pancreatic duct is the most often used model of acute severe necrotizing pancreatitis in rats. Ex vivo models allow to eliminate the influence of hormonal and nervous factors on the development of acute pancreatitis.

References

  • 1. Adler G., Gerhards G., Schick J., Rohr G., Kern H.F.: Effects of invivo cholinergic stimulation of rat exocrine pancreas. Am. J. Physiol.,1983; 244: G623-G629
    Google Scholar
  • 2. Aho H.J., Koskensalo S.M., Nevalainen T.J.: Experimental pancreatitisin the rat. Sodium taurocholate-induced acute haemorrhagicpancreatitis. Scand. J. Gastroenterol., 1980; 15: 411-416
    Google Scholar
  • 3. Aho H.J., Nevalainen T.J.: Experimental pancreatitis in the rat.Ultrastructure of sodium taurocholate-induced pancreatic lesions.Scand. J. Gastroenterol., 1980; 15: 417-424
    Google Scholar
  • 4. Barzilai A., Ryback B.J., Medina J.A., Toth L., Dreiling D.A.: Themorphological changes of the pancreas in hypovolemic shock andthe effect of pretreatment with steroids. Int. J. Pancreatol., 1987;2: 23-32
    Google Scholar
  • 5. Case R.M.: Is the rat pancreas an appropriate model of the humanpancreas? Pancreatology, 2006; 6: 180-190
    Google Scholar
  • 6. Dawra R., Sharif R., Phillips P., Dudeja V., Dhaulakhandi D., SalujaA.K.: Development of a new mouse model of acute pancreatitis inducedby administration of L-arginine. Am. J. Physiol. Gastrointest.Liver Physiol., 2007; 292: G1009-G1018
    Google Scholar
  • 7. Dembiński A., Warzecha Z., Ceranowicz P., Cieszkowski J., PawlikW.W., Tomaszewska R., Kuśnierz-Cabala B., Naskalski J.W., KuwaharaA., Kato I.: Role of growth hormone and insulin-like growth factor-1in the protective effect of ghrelin in ischemia/reperfusion-inducedacute pancreatitis. Growth Horm. IGF Res., 2006; 16: 348-356
    Google Scholar
  • 8. Dembiński A., Warzecha Z., Ceranowicz P., Stachura J., TomaszewskaR., Konturek S.J., Sendur R., Dembiński M., Pawlik W.W.: Pancreaticdamage and regeneration in the course of ischemia-reperfusioninduced pancreatitis in rats. J. Physiol. Pharmacol., 2001; 52: 221-235
    Google Scholar
  • 9. Dembiński A., Warzecha Z., Ceranowicz P., Tomaszewska R., StachuraJ., Konturek S.J., Konturek P.C.: Ghrelin attenuates the developmentof acute pancreatitis in rat. J. Physiol. Pharmacol., 2003; 54: 561-573
    Google Scholar
  • 10. Dembiński A., Warzecha Z., Konturek P.C., Ceranowicz P., StachuraJ., Tomaszewska R., Konturek S.J.: Epidermal growth factoraccelerates pancreatic recovery after caerulein-induced pancreatitis.Eur. J. Pharmacol., 2000; 398: 159-168
    Google Scholar
  • 11. Dressel T.D., Goodale R.L.Jr., Arneson M.A., Borner J.W.: Pancreatitisas a complication of anticholinesterase insecticide intoxication.Ann. Surg., 1979; 189: 199-204
    Google Scholar
  • 12. Fujimoto K., Hosotani R., Wada M., Lee J., Koshiba T., MiyamotoY., Doi R., Imamura M.: Ischemia-reperfusion injury on the pancreasin rats: identification of acinar cell apoptosis. J. Surg. Res., 1997;71: 127-136
    Google Scholar
  • 13. Griffith W.H., Wade N.J.: Choline metabolism. I. The occurrenceand prevention of hemorrhagic degeneration in young rats on a lowcholine diet. J. Biol. Chem., 1939; 131: 567-577
    Google Scholar
  • 14. Hoffmann T.F., Leiderer R., Waldner H., Arbogast S., Messmer K.:Ischemia reperfusion of the pancreas: a new in vivo model for acutepancreatitis in rats. Res. Exp. Med., 1995; 195: 125-144
    Google Scholar
  • 15. Hosokawa R., Kikuzaki K., Kimoto T., Matsuura T., Chiba D., WadamotoM., Sato Y., Maeda M., Sano A., Akagawa Y.: Controlled localapplication of basic fibroblast growth factor (FGF-2) accelerates thehealing of GBR. An experimental study in beagle dogs. Clin. Oral ImplantsRes., 2000; 11: 345-353
    Google Scholar
  • 16. Jaworek J., Leja-Szpak A., Dembiński A., Tomaszewska R., SzklarczykJ., Kot M., Nawrot-Porąbka K., Bonior J, Warzecha Z., PawlikW.W.: Involvement of sensory nerves in the protective effect ofgrowth hormone on acute pancreatitis. Growth Horm. IGF Res.,2009; 19: 517-22
    Google Scholar
  • 17. Ji B., Bi Y., Simeone D., Mortensen R.M., Logsdon C.D.: Humanpancreatic acinar cells lack functional responses to cholecystokininand gastrin. Gastroenterology, 2001; 121: 1380-1390
    Google Scholar
  • 18. Kanno H., Nose M., Itoh J., Taniguchi Y., Kyogoku M.: Spontaneousdevelopment of pancreatitis in the MRL/Mp strain of micein autoimmune mechanism. Clin. Exp. Immunol., 1992; 89: 68-73
    Google Scholar
  • 19. Kodama T.: A light and electron microscopic study on the pancreaticductal system. Acta Pathol. Jpn., 1983; 33: 297-321
    Google Scholar
  • 20. Lampel M., Kern H.F.: Acute interstitial pancreatitis in the ratinduced by excessive doses of a pancreatic secretagogue. VirchowsArch. A Pathol. Anat. Histol., 1977; 373: 97-117
    Google Scholar
  • 21. Lerch M.M., Gorelick F.S.: Models of acute and chronic pancreatitis.Gastroenterology, 2013; 144: 1180-1193
    Google Scholar
  • 22. Lerch M.M., Saluja A.K., Rünzi M., Dawra R., Saluja M., Steer ML.:Pancreatic duct obstruction triggers acute necrotizing pancreatitisin the opossum. Gastroenterology, 1993; 104: 853-861
    Google Scholar
  • 23. Lombardi B., Estes L.W., Longnecker D.S.: Acute hemorrhagicpancreatitis (massive necrosis) with fat necrosis induced in miceby DL-ethionine fed with a choline-deficient diet. Am. J. Pathol.,1975; 79: 465-480
    Google Scholar
  • 24. Manso M.A., Ramudo L., De Dios I.: Extrapancreatic organ impairmentduring acute pancreatitis induced by bile-pancreatic ductobstruction. Effect of N-acetylcysteine. Int. J. Exp. Pathol., 2007;88: 343-349
    Google Scholar
  • 25. Mantke R., Schubert D., Röcken C., Paege I., Halangk W., Peters B.,Lippert H., Schulz H.U.: Caerulein or taurocholate induced enzymaticand histologic alterations in the isolated perfused rat pancreas.Langenbecks Arch. Surg., 2009; 394: 363-369
    Google Scholar
  • 26. Miyasaka K., Shinozaki H., Jimi A., Funakoshi A.: Amylase secretionfrom dispersed human pancreatic acini: neither cholecystokinina nor cholecystokinin B receptors mediate amylase secretion in vitro.Pancreas, 2002; 25: 161-165
    Google Scholar
  • 27. Mizunuma T., Kawamura S., Kishino Y.: Effects of injecting excessarginine on rat pancreas. J. Nutr., 1984; 114: 467-471
    Google Scholar
  • 28. Mouret J.: Contribution a l´étude des cellules glandulaires (pancreas).J. Anat. Physiol., 1895; 31: 221-236
    Google Scholar
  • 29. Niederau C., Ferrell L.D., Grendell J.H.: Caerulein-induced acutenecrotizing pancreatitis in mice: protective effects of proglumide,benzotript, and secretin. Gastroenterology, 1985; 88: 1192-1204
    Google Scholar
  • 30. Ohshio G., Saluja A., Steer M.L.: Effects of short-term pancreaticduct obstruction in rats. Gastroenterology, 1991; 100: 196-202
    Google Scholar
  • 31. Ostrowski S.E., Reilly A.A., Collins D.N., Ramsingh A.I.: Progressionor resolution of coxsackievirus B4-induced pancreatitis: a genomicanalysis. J. Virol., 2004; 78: 8229-8237
    Google Scholar
  • 32. Pantoja J.L., Renner I.G., Abramson S.B., Edmondson H.A.: Productionof acute hemorrhagic pancreatitis in the dog using venomof the scorpion, Buthus quinquestriatus. Dig. Dis. Sci., 1983; 28: 429-439
    Google Scholar
  • 33. Pfeffer R.B., Lazzarini-Robertson A.Jr., Safadi D., Mixter G.Jr., SecoyC.F., Hinton J.W.: Gradations of pancreatitis, edematous, throughhemorrhagic, experimentally produced by controlled injection ofmicrospheres into blood vessels in dogs. Surgery, 1962; 51: 764-769
    Google Scholar
  • 34. Pfeffer R.B., Stasior O., Hinton J.W.: The clinical picture of thesequential development of acute hemorrhagic pancreatitis in thedog. Surg. Forum, 1957; 8: 248-251
    Google Scholar
  • 35. Sah R.P., Dawra R.K., Saluja A.K.: New insights into the pathogenesisof pancreatitis. Curr. Opin. Gastroenterol., 2013; 29: 523-530
    Google Scholar
  • 36. Saharia P., Margolis S., Zuidema G.D., Cameron J.L.: Acute pancreatitiswith hyperlipemia: studies with an isolated perfused caninepancreas. Surgery, 1977; 82: 60-67
    Google Scholar
  • 37. Saluja A., Saluja M., Villa A., Leli U., Rutledge P., Meldolesi J.,Steer M.: Pancreatic duct obstruction in rabbits causes digestivezymogen and lysosomal enzyme colocalization. J. Clin. Invest., 1989;84: 1260-1266
    Google Scholar
  • 38. Schmid S.W., Uhl W., Kidd M., Modlin I.M., Büchler M.W.: Experimentalmodels of acute pancreatitis and their clinical relevance.W: Acute pancreatitis. Novel concepts in biology and therapy, red.:M.W. Büchler, W. Uhl, H. Friess, P. Malfertheiner. Blackwell Wissenschafts-VerlagGmbH, Berlin-Vienna 1999, 51-62
    Google Scholar
  • 39. Shibayama Y.: Pancreatic venous stasis and endotoxaemia asaetiologic factors in acute haemorrhagic pancreatitis. J. Pathol.,1987; 152: 177-182
    Google Scholar
  • 40. Sporek M., Kolber W., Kuśnierz-Cabala B., Dumnicka P., Gurda–Duda A., Kuźniewski M., Solnica B., Kulig J.: Determination of hepatocytegrowth factor at early phase of acute pancreatitis. FoliaMed. Cracov., 2013; 53: 87-95
    Google Scholar
  • 41. Tamura K., Manabe T., Kyogoku T., Andoh K., Ohshio G., Tobe T.:Effect of postischemic reperfusion on the pancreas. Hepatogastroenterology,1993; 40: 452-456
    Google Scholar
  • 42. Thal A., Brackney E.: Acute hemorrhagic pancreatic necrosisproduced by local Shwartzman reaction: experimental study onpancreatitis. J. Am. Med. Assoc., 1954; 155: 569-574
    Google Scholar
  • 43. Thal A., Molestina J.E.: Studies on pancreatitis. III. Fulminatinghemorrhagic pancreatic necrosis produced by means of staphylococcaltoxin. AMA Arch. Pathol., 1955; 60: 212-220
    Google Scholar
  • 44. Truty M.J., Smoot R.L.: Animal models in pancreatic surgery:a plea for pork. Pancreatology, 2008; 8: 546-550
    Google Scholar
  • 45. Ueda T., Takeyama Y., Hori Y., Shinkai M., Takase K., GoshimaM., Yamamoto M., Kuroda Y.: Hepatocyte growth factor increases ininjured organs and functions as an organotrophic factor in rats withexperimental acute pancreatitis. Pancreas, 2000; 20: 84-93
    Google Scholar
  • 46. Ueda T., Takeyama Y., Toyokawa A., Kishida S., Yamamoto M.,Saitoh Y.: Significant elevation of serum human hepatocyte growthfactor levels in patients with acute pancreatitis. Pancreas, 1996;12: 76-83
    Google Scholar
  • 47. Ursing B.: Acute pancreatitis in coxsackie B infection. Br. Med.J., 1973; 3: 524-525
    Google Scholar
  • 48. Vollmar B., Waldner H., Schmand J. Conzen P.F., Goetz A.E., HabazettlH., Schweiberer L., Brendel W.: Oleic acid induced pancreatitisin pigs. J. Surg. Res., 1991; 50: 196-204
    Google Scholar
  • 49. Watanabe O., Baccino F.M., Steer M.L., Meldolesi J.: Supramaximalcaerulein stimulation and ultrastructure of rat pancreaticacinar cell: early morphological changes during development ofexperimental pancreatitis. Am. J. Physiol., 1984; 246: G457-G467
    Google Scholar
  • 50. Warzecha Z., Ceranowicz P., Dembinski A., Cieszkowski J., Kusnierz-CabalaB., Tomaszewska R., Kuwahara A., Kato I.: Therapeuticeffect of ghrelin in the course of cerulein-induced acute pancreatitisin rats. J. Physiol. Pharmacol., 2010; 61: 419-427
    Google Scholar
  • 51. Warzecha Z., Dembiński A.: Protective and therapeutic effectsof ghrelin in the gut. Curr. Med. Chem., 2012; 19: 118-125
    Google Scholar
  • 52. Warzecha Z., Dembiński A., Ceranowicz P., Konturek S.J., TomaszewskaR., Stachura J., Konturek P.C.: IGF-1 stimulates productionof interleukin-10 and inhibits development of caerulein-inducedpancreatitis. J. Physiol. Pharmacol., 2003; 54: 575-590
    Google Scholar
  • 53. Warzecha Z., Dembiński A., Ceranowicz P., Konturek S.J., TomaszewskaR., Stachura J., Nakamura T., Konturek P.C.: Inhibitionof cyclooxygenase-2 reduces the protective effect of hepatocytegrowth factor in experimental pancreatitis. Eur. J. Pharmacol., 2004;486: 107-119
    Google Scholar
  • 54. Warzecha Z., Dembiński A., Konturek P.C., Ceranowicz P., KonturekS.J.: Epidermal growth factor protects against pancreatic damagein cerulein-induced pancreatitis. Digestion, 1999; 60: 314-323
    Google Scholar
  • 55. Warzecha Z., Dembiński A., Konturek P.C., Ceranowicz P., KonturekS.J., Tomaszewska R., Schuppan D., Stachura J., Nakamura T.:Hepatocyte growth factor attenuates pancreatic damage in caerulein-inducedpancreatitis in rats. Eur. J. Pharmacol., 2001; 430: 113-121
    Google Scholar
  • 56. Weinbroum A.A.: Mannitol prevents acute lung injury afterpancreas ischemia-reperfusion: a dose-response, ex vivo study. Lung,2009; 187: 215-224
    Google Scholar
  • 57. Yuan Z., Meyerholz D.K., Twait E.C., Kempuraj D., Williard D.E.,Samuel I.: Systemic inflammation with multiorgan dysfunction isthe cause of death in murine ligation-induced acute pancreatitis. J.Gastrointest. Surg., 2011; 15: 1670-1678
    Google Scholar

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