Skip to main content
Log in

Salutary and prophylactic effect of pentadecapeptide BPC 157 on acute pancreatitis and concomitant gastroduodenal lesions in rats

  • Pancreatic And Biliary Disorders
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

The superior effectiveness of a new pentadecapeptide, BPC 157, on gastrointestinal and liver lesions, in conjunction with an antiinflammatory and analgetic activity was recently noted. In the present study, BPC 157 was tested as either a protective or healing agent in bile duct ligation-induced acute pancreatitis in rats. In addition, the positive influence of BPC 157 on concomitantly developed gastric and duodenal lesions was simultaneously investigated. BPC 157 (10 µg, 10 ng/kg body wt, intraperitoneally or intragastrically) was given prophylactically 1 hr before ligation, whereas the therapy was given once daily beginning with the 24 hr following ligation (last application 24 hr before killing). The effect was investigated at daily intervals until the end of the fifth day after ligation. In the pretreatment regimen, a strong pancreas protection was obtained. When applied in the condition of already established severe acute pancreatitis, an obvious salutary effect was consistently noted. Assessing the appearance of the necrosis, edema, neutrophils, and mononuclears, consistently less necrosis, edema, and neutrophils, but more mononuclears, were found in BPC-treated rats. Likewise, in studies of the serum amylase values, relative to control data, a markedly lower rise (BPC pretreatment regimen) as well as a worsening of the already raised values (BPC therapy regimen) was noted. Along with its beneficial effect on pancreatitis, a positive influence of BPC 157 on the gastric and duodenal lesion course in bile duct-ligated rats was noted in both the pre- and posttreatment regimen. Taken together, in further studies of acute pancreatitis therapy, BPC could be an interesting and useful agent with an additional positive impact on concomitant gastroduodenal pathology.

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.

Institutional subscriptions

Similar content being viewed by others

References

  1. Geokas MC, Baltaxe HA, Banks PA, Silva J, Frey CF: Acute pancreatitis. Ann Intern Med 103:86–100, 1985

    Google Scholar 

  2. Pár A: Free radical mechanisms in gastrointestinal and liver diseases. A review. Exp Clin Gastroenterol 2:162–173, 1992

    Google Scholar 

  3. Durr GHK: Therapeutic trials in acute pancreatitis. German experience. Gastroenterol Clin Biol 11:951–954, 1978

    Google Scholar 

  4. Imrie CW, Blumgart LH: Glucagon therapy in acute pancreatitis. Br Med J 11:38–39, 1974

    Google Scholar 

  5. MCR Multicentre Trial: Death from acute pancreatitis. Lancet 2:632, 1977

    Google Scholar 

  6. Thompson J, Greeley GH Jr, Rayford PL, Twonsed CM Jr: Gastrointestinal Endocrinology. New York, McGraw-Hill, 1987

    Google Scholar 

  7. Schwedes U, Althoff PH, Klempa L, Leuschner L, Mothes L, Raptis S, Wdowinski J, Usadel KH: Effect of somatostatin on bile induced acute haemorrhagic pancreatitis in the dog. Horm Metab Res 11:655–658, 1977

    Google Scholar 

  8. Baxter JN, Jenkens SA, Day DW, Roberts DC, Cowelt DC, Mackie CR, Shields R: Effects of somatostatin and a long-acting somatostatin analogue on the prevention and treatment of experimentally induced acute pancreatitis in rat. Br J Surg 72:382–385, 1985

    Google Scholar 

  9. Lankish PG, Koop H, Wincker K, Folsch UR, Creutzfeld W: Somatostatin therapy of acute pancreatitis. Gut 18:713–716, 1977

    Google Scholar 

  10. Papp M: Pancreatic cytoprotection: new approaches.In Cell Injury and Protection in the Gastrointestinal Tract: From Basic Sciences to Clinical Perspectives. Gy Mózsik, A Pá, G Csomós, M Kitajima, M Kondo, CJ Pfeiffer, KD Rainsford, P Sikiric, S Szabo (eds). Budapest, Akedémiai Kiadó, 1992, pp 399–406

    Google Scholar 

  11. Kusterer K, Enghofer M, Poschmann T, Usadel KH: The effect of somatostatin, gabexate mesilate and dextran 40 on the microcirculation in sodium taurocholate-induced pancreatitis.In Cell Injury and Protection in the Gastrointestinal Tract: From Basic Sciences to Clinical Perspectives. Gy Mózsik, A Pár, G Csomós, M Kitajima, M Kondo, CJ Pfeiffer, KD Rainsford, P Sikiric, S Szabo (eds). Budapest, Akedémiai Kiadó, 1992, pp 407–415

    Google Scholar 

  12. Manabe T, Steer ML: Protective effect of PGE2 on diet-induced acute pancreatitis in mice. Gastroenterology 78:777–781, 1980

    Google Scholar 

  13. Ebbehøj N, Fris J, Svenosen LB, Bullow S, Madsen P: Indomethacin treatment of acute pancreatitis. A controlled double blind trial. Scand J Gastroenterol 20:798–800, 1985

    Google Scholar 

  14. Thorner MO: Dopamine is an important neurotransmitter in the autonomic system. Lancet 1:662–667, 1975

    Google Scholar 

  15. Sikiric P, Rotkvic I, Mise S, Krizanac S, Gjuris V, Jagic V, Suchanek E, Petek M, Udovicic I, Geber J, Tucan-Foretic M, Cvitanovic B, Ivanovic D, Marovic A: The influence of dopamine receptor agonists and an antagonists on acute pancreatitis in rats. Eur J Pharmacol 147:321–326, 1988

    Google Scholar 

  16. Hernandez DE, Walker CH, Valenzuela JE, Mason GA: Increased dopamine receptor binding in duodenal mucosa of duodenal ulcer patients. Dig Dis Sci 34:543–547, 1989

    Google Scholar 

  17. Hernandez DE: Neuroendocrine mechanisms of stress ulceration: Focus on thyrotropin releasing hormone (TRH). Life Sci 39:279–296, 1986

    Google Scholar 

  18. Sikiric P, Geber J, Ivanovic D, Suchanek E, Gjuris V, Tucan-Foretic M, Mise S, Cvitanovic B, Rotkvic I: Dopamine antagonists induce gastric lesions in rats. Eur J Pharmacol 131:105–109, 1986

    Google Scholar 

  19. Sikiric P, Rotkvic I, Mise S, Krizanac S, Gjuris V, Jukic J, Suchanek E, Petek M, Udovicic I, Kalogjera L, Geber J, Tucan-Foretic M, Duvnjak M, Philipp M, Balen I, Anic T: The influence of dopamine agonists and antagonists on indomethacin lesions in stomach and small intestine in rats. Eur J Pharmacol 158:61–67, 1988

    Google Scholar 

  20. Sikiric P, Rotkvic I, Mise S, Petek M, Rucman R, Seiwerth S, Zjacic Rotkvic V, Duvnjak M, Jagic V, Suchanek E, Grabarevic Z, Anic T, Brkic T, Djermanovic Z, Dodig M, Marovic A, Hernandez DE: Dopamine agonists prevent duodenal ulcer relapse: A comparative study with famotidine and cimetidine. Dig Dis Sci 36:905–910, 1991

    Google Scholar 

  21. Sikiric P, Petek M, Rucman R, Rotkvic I, Seiwerth S, Grabarevic Z, Suchanek E, Jagic V, Krnjevic H, Mise S, Duvnjak M, Turkovic B, Udovicic I: Hypothesis: Stomach stress response, diagnostic and therapeutical value: a new approach in organoprotection. Exp Clin Gastroenterol 1:15–16, 1991

    Google Scholar 

  22. Sikiric P, Petek M, Rucman R, Grabarevic Z, Seiwerth S, Rotkvic I, Jagic V, Danilovic Z, Dodig M, Duvnjak M, Artukovic B, Dzaja P, Senecic I, Suchanek E, Giljanovic S, Mise S, Djarmanovic Z: Beneficial effect of a new gastric juice peptide, body protection compound, in acute pancreatitis models. Exp Clin Gastroenterol 1:24–25, 1991

    Google Scholar 

  23. Sikiric P, Petek M, Rucman R, Rotkvic I, Seiwerth S, Grabarevic Z, Jagic V, Turkovic B, Mildner B, Duvnjak M, Cviko A, Kolega M, Dodig M, Sallmani A, Djacic S, Lucinger D, Erceg D: The significance of the gastroprotective effect of body protection compound (BPC): Modulation by different procedures.In Cell Injury and Protection in the Gastrointestinal Tract: From Basic Sciences to Clinical Perspectives. Gy Mózsik, A Pár, G Csomós, M Kitajima, M Kondo, CJ Pfeiffer, KD Rainsford, P Sikiric, S Szabo (eds). Budapest, Akedémiai Kiadó, 1992, pp 89–98

    Google Scholar 

  24. Sikiric P, Petek M, Rucman R, Seiwerth S, Grabarevic Z, Rotkvic I, Jagic V, Mildner B, Duvnjak M, Lang N: A new gastric juice peptide, BPC—an overview of stomach/stress organoprotection hypothesis and BPC beneficial effects. J Physiol (Paris) 87:313–327, 1993

    Google Scholar 

  25. Sikiric P, Seiwerth S, Grabarevic Z, Rucman R, Petek M, Rotkvic I, Turkovic B, Jagic V, Mildner B, Duvnjak M, Danilovic Z: Hepatoprotective effect of BPC 157, a 15-amino acid peptide, on liver lesions induced by either restraint stress or bile duct and hepatic artery ligation or CCl4 administration. A comparative study with dopamine agonists and somatostatin. Life Sci 53:PL291-PL296, 1993

    Google Scholar 

  26. Sikiric P, Gyires K, Seiwerth S, Grabarevic Z, Rucman R, Petek M, Rotkvic I, Turkovic B, Udovicic I, Jagic V, Mildner B, Duvnjak M, Danilovic Z: The effect of pentadecapeptide BPC 157 on inflammatory, non-inflammatory, direct and indirect pain and capsaicin neurotoxicity. Inflammopharmacology 2:121–127, 1993

    Google Scholar 

  27. Sikiric P, Seiwerth S, Grabarevic Z, Petek M, Rucman R, Turkovic B, Rotkvic I, Jagic V, Duvnjak M, Mise S, Djacic S, Separovic J, Veljaca M, Sallmani A, Banic M, Brkic T: The beneficial effect of BPC 157, a 15 amino acid peptide BPC fragment, on gastric and duodenal lesions induced by restraint stress, cysteamine and 96% ethanol in rats. A comparative study with H2 receptor antagonists, dopamine promoters and gut peptides. Life Sci 54:PL63-PL68, 1994

    Google Scholar 

  28. Seiwerth S, Grabarevic Z, Danilovic Z, Djacic S, Sikiric P, Cviko A, Kolega M: The influence of BPC 157 on incisional wound healing. Pathol Res Pract 189:809–810, 1993

    Google Scholar 

  29. Mózsik Gy, Sikiric P, Petek M: Gastric mucosal preventing body protective compound (BPC) effect on the development of ethanol and HCl-induced gastric mucosal injury. Exp Clin Gastroenterol 1:87–90, 1991

    Google Scholar 

  30. Paré W, Klucyznski JM: The effect of new gastric juice peptide BPC on classic stress triad in stress procedure. Exp Clin Gastroenterol 2:234–236, 1992

    Google Scholar 

  31. Veljaca M, Pllana R, Lesch CA, Sanchez B, Chan K, Guglietta A: Protective effect of BPC 157 on a rat model of colitis. Gastroenterology 106:789, 1994

    Google Scholar 

  32. Veljaca M, Lech CA, Pllana R, Sanchez B, Chan K, Guglietta A: BPC-15 reduces trinitrobenzene sulfonic acid-induced colonic damage in rats. J Pharmacol Exp Ther 272:417–422, 1994

    Google Scholar 

  33. Veljaca M, Lesch CA, Sanchez B, Low J, Guglietta A: Protection of BPC-15 on TNBS-induced colitis in rats: Possible mechanisms of action. Gastroenterology 108:936, 1995

    Google Scholar 

  34. Bosnjak ZJ, Graf BM, Sikiric P, Stowe DF: Protective effects of newly isolated gastric peptide following hypoxic and reoxygenation injury in the isolated guinea pig heart. FASEB J 8:A129, 1994

    Google Scholar 

  35. Veljaca M, Chan K, Guglietta A: Digestion of h-EGF, h-TGF alpha, and BPC-15 in human gastric juice. Gastroenterology 108:761, 1995

    Google Scholar 

  36. Sikiric P, Seiwerth S, Grabarevic Z, Rotkvic I, Jagic V, Mise S, Duvnjak M, Artukovic B, Brkic H, Vukovic S, Banic M, Brkic T, Djermanovic Z, Dodig M, Bacic M, Marovic A, Uglesic M: Comparison between the effects of dopamine drugs on gastric liver lesions induced in two suitable experimental rat models. Dig Dis Sci 35:1567, 1990

    Google Scholar 

  37. Ceska M, Hultman E, Ingelman BGA: A new method for determination of alfa-amylase. Experientia 25:555–556, 1969

    Google Scholar 

  38. Eastham RD: Biochemical values in clinical medicine. London, John Wright & Son, 1978

    Google Scholar 

  39. Guglietta A: Possible clinical use of peptide growth factors in the GI tract: Perspectives and obstacles. Exp Clin Gastroenterol 3:1–6, 1993

    Google Scholar 

  40. Szabo S, Trier JS, Brown A, Schnoor J: Early vascular injury and increased vascular permeability in gastric mucosal injury caused by ethanol in the rat. Gastroenterology 88:228–236, 1985

    Google Scholar 

  41. Krieger DT: Brain peptides: What, where and why? Science 222:975–985, 1983

    Google Scholar 

  42. Snyder SH: Brain peptides as neurotransmitters. Science 209:976–983, 1980

    Google Scholar 

  43. Heiling M, Murison R: Intracerebroventricular neuropeptide Y protects against stress-induced gastric lesions in rat. Eur J Pharmacol 137:127–129, 1987

    Google Scholar 

  44. Szabo S, Usadel KH: Cytoprotection-organoprotection by somatostatin: Gastric and hepatic lesions. Experientia 38:254–256, 1982

    Google Scholar 

  45. Sikiric P, Rotkvic I, Mise S, Seiwerth S, Grabarevic Z, Petek M, Rucman R, Zjacic-Rotkvic V, Duvnjak M, Jagic V, Suchanek E, Marovic A, Banic M, Brkic T, Hanzevacki M, Separovic J, Djacic S, Simicevic V: Dopamine agents efficacy in peptide ulcer healing and relapse prevention—a further indication for importance of stomach dopamine in the stress organoprotection concept.In Neuroendocrinology of Gastrointestinal Ulceration: Hans Selye Symposia on Neuroendocrinology and Stress, Vol 2., S Szabo, Y Taché, G Glavin (eds). New York, Plenum Press, 1995, pp 221–230

    Google Scholar 

  46. Senecic I, Sikiric P, Giljanovic S: The effects of somatostatin on stress-induced gastric lesions in mice. Exp Clin Gastroenterol 1:171–173, 1991

    Google Scholar 

  47. Guth PH, Mecriff JC, Paulsen G: Prevention by glucagon of experimental stress induced hemorrhagic gastritis. Gastroenterology 69:1048–1050, 1975

    Google Scholar 

  48. Robert A: Cytoprotection by prostaglandins. Gastroenterology 77:761–767, 1979

    Google Scholar 

  49. Schmidt KL, Miller TA: Cytoprotection: Fact or fancy? The morphologic basis of gastric protection by prostaglandins. Exp Clin Gastroenterol 1:119–132, 1991

    Google Scholar 

  50. Szabo S, Neumeyer JL: Dopamine agonists and antagonists in duodenal ulcer disease.In ACS Symposium Series. C Kaiser, W Kebabian (eds). Washington, DC, American Chemical Society, 1983, pp 175–196

    Google Scholar 

  51. Sikiric P, Rotkvic I, Mise S, Kriznac S, Suchanek E, Petek M, Gjuris V, Tucan-Foretic M, Udovicic I, Anic T, Balen I: The influence of dopamine agonists and antagonists on gastric lesions in mice. Eur J Pharmacol 144:237–239, 1987

    Google Scholar 

  52. Shwartz TW: Enteroinsular axis of pancreatic polypeptide. Front Horm Res 7:82–91, 1980

    Google Scholar 

  53. Langman MSJ, Cooke AR: Gastric and duodenal ulcer and their associated diseases. Lancet 1:680–683, 1976

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This study was subsidized by grants from the Ministry of Science of the Republic of Croatia and Pliva, Zagreb, Croatia.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sikirić, P., Seiwerth, S., Grabarević, Ž. et al. Salutary and prophylactic effect of pentadecapeptide BPC 157 on acute pancreatitis and concomitant gastroduodenal lesions in rats. Digest Dis Sci 41, 1518–1526 (1996). https://doi.org/10.1007/BF02088582

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02088582

Key words

Navigation