Archive for Liver

BPC 157. ATTENUATED GASTRIC ULCERS, SEIZURES, BRAIN LESIONS, HEPATOMEGALY, FATTY LIVER

This trial shows the effectiveness of BPC157 on damages caused by insulin over dosage, which can be very useful for diabetics who inject themselves too much insulin… extracts:

 

OVER-DOSE INSULIN AND STABLE GASTRIC PENTADECAPEPTIDE BPC 157. ATTENUATED GASTRIC ULCERS, SEIZURES, BRAIN LESIONS,  HEPATOMEGALY, FATTY LIVER, BREAKDOWN OF LIVER GLYCOGEN, PROFOUND HYPOGLYCEMIA AND CALCIFICATION IN RATS

 

INTRODUCTION

The general significance of insulin induced ulcers remains not determined. We focused on hyperinsulinemia, deliberate injection of excessive insulin, and possibility that an anti-ulcer therapy with anti-ulcer peptide may be more successful counteracting therapy.

Insulin induced ulcers were long ago described, and related to gastric acid hypersecretion (1, 2).

Thus, to provide some novel intriguing insights, we focused on insulin induced gastric ulcers (1, 2) and then on other disturbances that may be concomitantly induced by insulin application (3-5).

 

We focused on a peptide therapy, using a small, orally active, anti-ulcer peptide (7-11) stable gastric pentadecapeptide BPC 157 (MW 1419) with very safe profile (LD1 could be not achieved, no side effects in clinical trials (12, 13) stable in human gastric juice (14), effective in trials for inflammatory bowel disease therapy (12, 13) and wound healing (15-18) also in diabetic rats (18, 19).

Importantly, pentadecapeptide BPC 157 was more active than recombinant human platelet-derived growth factor (PDGF-BB), stimulating both expression of early growth response 1 (egr-1) gene and its repressor nerve growth factor 1- A binding protein-2 (NAB2) (18).

Thereby, it may be important for cytokine induction, growth factor generation, early extracellular matrix (collagen) formation (18), but also for gluconeogenesis regulation (20).

Finally, alloxan-gastric ulcers in rats and mice may be inhibited by stable gastric pentadecapeptide BPC 157 (21).

 

DISCUSSION

Thus, when given to insulin-rats, BPC 157 would be confronted with the all processes simultaneously occurring that eventually lead to stomach ulcer (1, 2), hypoglycemia and all mentioned disturbances and death in insulin over-dose-rats (3-5). However, we shown that pentadecapeptide BPC 157, as an antiulcer peptide (7-11), may besides stomach ulcer consistently counteract all insulin disturbances and fatal outcome. This may also indicate that these disturbances are also interconnected throughout BPC 157 background. Moreover, considering the used insulin (250 IU/kg i.p.) /BPC 157 (10 µg, 10 ng/kg i.p. or i.g.) ratio (7, 8), it may be reasonably to assume that these therapy effects may indicate a likely role of BPC 157 in insulin controlling and influence on one or more causative process(es).

 

In conclusion, these findings demonstrate that when one application of very high dose of insulin may induce together stomach ulcer, seizures, severely damaged neurons in cerebral cortex and hippocampus, hepatomegaly, fatty liver, breakdown of liver glycogen with profound hypoglycemia, along with calcium deposition, and finally fatal outcome in rats, all damages were markedly attenuated when BPC 157 was applied.

The same effectiveness when given intraperitoneally or intragastrically (i.e., stable in human gastric juice (14)) may be suggestive that BPC 157 may have also an incretin role in controlling insulin effects (7, 8, 11).

Intriguingly, further studies may show whether standard anti-ulcer agents that prevent insulin-stomach ulcer (1, 2) may also have a broader beneficial effect on other disturbances presented in insulin-rats.

Previously, BPC 157 was shown to counteract toxic effects of other insulin preparations (43).

 

Source for this article: http://www.jpp.krakow.pl/journal/archive/12_09_s7/articles/13_article.html

 

Useful References:

  • 7. Sikiric P, Petek M, Rucman R, et al. A new gastric juice peptide, BPC. An overview of the stomach-stress-organoprotection hypothesis and beneficial effects of BPC. J Physiol (Paris) 1993; 87: 313-327.
  • 8. Sikiric P, Seiwerth S, Brcic L, et al. Stable gastric pentadecapeptide BPC 157 in trials for inflammatory bowel disease (PL-10, PLD-116, PL 14736, Pliva, Croatia). Full and distended stomach, and vascular response. Inflammopharmacology 2006; 14: 214-221.
  • 9. Sikiric P, Siwerth S, Grabarevic Z, et al. The beneficial effect of BPC 157, a 15 amino acid peptide BPC fragment, on gastric and duodenal lesion induced by restraint stress, cysteamine and 96% ethanol in rats. A comparative study with H2 receptor antagonists, dopamine promoters and gut peptides. Life Sci 1994; 54: 63-68.
  • 10. Sikiric P, Seiwerth, S, Grabarevic Z, et al. The influence of a novel pentadecapeptide, BPC 157, on N(G)-nitro-L-arginine methylester and L-arginine effects on stomach mucosa integrity and blood pressure. Eur J Pharmacol 1997; 332: 23-33.
  • 11. Sikiric P, Seiwerth S, Grabarevic Z, et al. Salutary and prophylactic effect of pentadecapeptide BPC 157 on acute pancreatitis and concomitant gastroduodenal lesions in rats. Dig Dis Sci 1996; 41: 1518-1526.
  • 12. Veljaca M, Pavic-Sladoljev D, Mildner B, et al. Safety, tolerability and pharmacokinetics of PL 14736, a novel agent for treatment of ulcerative colitis, in healthy male volunteers. Gut 2003; 51: A309.
  • 13. Ruenzi M, Stolte M, Veljaca M, Oreskovic K, Peterson J. A multicenter, randomized, double blind, placebo-controlled phase II study of PL 14736 enema in the treatment of mild-to-moderate ulcerative colitis. Gastroenterology 2005; 128: A584.
  • 14. Veljaca M, Chan K, Guglietta A. Digestion of h-EGF, h-TGF alpha and BPC 157 in human gastric juice. Gastroenterology 1995; 108: 761.
  • 15. Sikiric P, Seiwerth S, Mise S, et al. Corticosteroid-impairment of healing and gastric pentadecapeptide BPC-157 creams in burned mice. Burns 2003; 29: 323-334.
  • 16. Novinscak T, Brcic L, Staresinic M, et al. Gastric pentadecapeptide BPC 157 as an effective therapy for muscle crush injury in the rat. Surg Today 2008; 38: 716-725.
  • 17. Staresinic M, Petrovic I, Novinscak T, et al. Effective therapy of transected quadriceps muscle in rat: gastric pentadecapeptide BPC 157. J Orthop Res 2006; 24: 1109-1117.
  • 18. Tkalcevic VI, Cuzic S, Brajsa K, et al. Enhancement by PL 14736 of granulation and collagen organization in healing wounds and the potential role of egr-1 expression. Eur J Pharmacol 2007; 570(1-3): 212-221.
  • 20. Berasi SP, Huard C, Li D, et al. Inhibition of gluconeogenesis through transcriptional activation of EGR1 and DUSP4 by AMP-activated kinase. J Biol Chem 2006; 281: 27167-27177.
  • 21. Petek M, Sikiric P, Anic T, et al. Pentadecapeptide BPC 157 attenuates gatric lesions induced by alloxan in rats and mice. J Physiol (Paris) 1999; 93: 501-504.
  • 43. Ilic S, Mester M, Filipovic M, et al. Stable gastric pentadecapeptide BPC 157 and insulin induced gastric lesions in rats. J Physiol Pharmacol 2009; 60(Suppl 2): 40.

Pharmacological properties of peptide BPC 157

This trial demonstrates the multi-capabilities of BPC157 to repair and protect numerous organs in our body.

 

Inflammopharmacology-Journal

Inflammo Pharmacology Journal
March 1999, Volume 7, Issue 1, pp 1-14

Abstract

The reported beneficial effects of the gastric mucosal derived pentadecapeptide BPC 157 (Gly Glu Pro Pro Pro Gly Lys Pro Ala Asp Asp Ala Gly Leu Val, M.W. 1419) on different organ lesions are reviewed.

Apart from the effects on various gastrointestinal lesions, the potentially beneficial effect on pancreas, liver injuries, endothelium and heart damage, i.e. dysrhythmias following reoxygenation, and blood pressure, along with effect on experimental acute/chronic inflammation, wound and fracture (pseudoarthrosis) healing are described.

It appears that these beneficial effects all together provide a particular network reflecting activity of a special peptidergic defence system. In support of this concept, it appears that there are interactions of this pentadecapeptide with many important systems (namely, dopamine-, NO-, prostaglandin-, somatosensory neurone-systems), that could provide a basis for the observed protective effects. Moreover, since disturbance of these systems’ functions (i.e. dopamine-, NO-, somatosensory neuronal-system) which manifest either over-activity or as inhibition, may contribute to the multiple lesions in different organs.

The reported evidence that this pentadecapeptide is able to counteract both their over-action, and their inhibition, may suggest this pentadecapeptide as a new, but most probably essential physiological defence system and that should be further investigated.

 

Key words:
BPC 157 (PL-10) gastrointestinal lesions acute pancreatitis liver lesions inflammation and pain heart blood pressure behaviour physiological defence system

Source for this article: http://link.springer.com/article/10.1007%2Fs10787-999-0022-z

 

Useful Cited References:

  • 2. Sikiric, P., Petek, M., Rucman, R., etal. (1993). A new gastric juice peptide BPC — an overview of stomach/stress/organoprotection hypothesis and BPC beneficial effects, J. Physiol. (Paris) 87,313–327.
  • 3. Sikiric, P., Gyires, K., Seiwerth, S., et al. (1993). The effect of pentadecapeptide BPC 157 on inflammatory, non-inflammatory, direct and indirect pain and capsaicin neurotoxicity, Inflammopharmacology 2, 121–127.
  • 4. Sikiric, P., Banic, M., Brkic, T., et al. (1993). Effects of a novel pentadecapeptide BPC 157 and methylprednisolone in a murine model of inflammatory bowel disease, Gastroenterology 104, 782.
  • 5. Sikiric, P., Seiwerth, S., Grabarevic, Z., et al. (1993). Hepatoprotective effect of BPC 157, a 15-aminoacid peptide, on liver lesions induced by either restraint stress or bile duct and hepatic artery ligation or CCI4 application. A comparative study with dopamine agonists and somatostatin, Life Sci. 53, PL291-PL296.
  • 6. Sikiric, P., Seiwerth, S., Grabarevic, Z., et al. (1994). The beneficial effect of BPC 157, a 15 aminoacid 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 promotors and gut peptides, Life Sci. 54, PL63-PL68.
  • 7. Sikiric, P., Rotkvic, I., Mise, S. et al. (1995). Dopamine agents efficacy in peptic 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, Szabo, S., Taché, Y. and Glavin, G. (Eds), Vol. 2, pp. 221–230. Plenum, New York.
  • 8. Sikiric, P., Seiwerth, S., Grabarevic, Z., et al. (1996). Salutary and prophylactic effect of pentadecapeptide BPC 157 on acute pancreatitis and concomitant gastroduodenal lesions in rats, Digestive Disease Sci. 41, 1518–1526.
  • 9. Sikiric, P., Seiwerth, S., Grabarevic, Z., et al. (1996). The beneficial effect of a novel pentadecapeptide BPC 157 on gastric lesions induced by restraint stress, ethanol, indomethacin and capsaicin neurotoxicity, Digestive Disease Sci. 41, 1604–1614.
  • 10. Sikiric, P., Mazul, B., Seiwerth, S., et al. (1997). Pentadecapeptide BPC 157 interactions with adrenergic and dopaminergic systems in mucosal protection in stress, Digestive Disease Sci. 42, 661–671.
  • 11. Sikiric, P., Mikus, D., Seiwerth, S., et al. (1997). Pentadecapeptide BPC 157, cimetidine, ranitidine, bromocriptine and atropine effect in cysteamine lesions in totally gastrectomized rats. A model study for cytoprotective studies, Digestive Disease Sci. 42, 1029–1037.
  • 12. Sikiric, P., Seiwerth, S., Grabarevic, Z., et al. (1997). The influence of a novel pentadecapeptide BPC 157 on NG-nitro-L~arginine methylester and L-arginine effect on stomach mucosal integrity and blood pressure, European J. Pharmacol. 332, 23–33.
  • 13. Grabarevic, Z., Tisljar, M., Artukovic, B., et al. (1997). The influence of BPC 157 on nitric oxide agonists and antagonist induced lesions in broiler chicks, J. Physiol. (Paris) 91, 139–150.
  • 15. Jelovac, N., Sikiric, P., Rucman, R., et al. (1998). A novel pentadecapeptide BPC 157 blocks the stereotypy produced acutely by amphetamine and the developement of haloperidol-induced supersensitivity to amphetamine, Biol. Psych. 43, 511–519.CrossRef
  • 16. Konjevoda, P., Nasic, M., Curkovic, T, Sikiric, P., Seiwerth, S. and Stambuk, N. (1998). Effects of BPC 157 on the healing of corneal lesions, in: Uveitis Today, Ohno, S., Aoki, K., Usui, M. and Uchio, E. (Eds), pp. 311–314. Elsevier, Amsterdam.
  • 17. Kalogjera, L., Ries, N., Baudoin, T., Ferencic, Z., Protic, R. and Pegan, B. (1997). Dose dependent protective effect of BPC 157 in capasaicin induced rhinitis in rats, European Arch. Otorhinolaryngol. 254, S9-S11.
  • 18. Sikiric, P., Seiwerth, S., Grabarevic, Z., et al. (1997). Pentadecapeptide BPC 157 positively affects both non-steroidal anti-inflammatory agents-induced gastrointestinal lesions and adjuvant arthritis in rats, J. Physiol. (Paris) 91, 113–122.
  • 20. Sebecic, B., Nikolic, V., Sikiric, P. et al. (1999). Osteogenic effect of a gastric pentadecapeptide BPC 157, on the healing of segmental bone defect in rabbits. A comparison with bone marrow and autologous cortical bone implantation, Bone 24, 195–202.
  • 21. Zoricic, I., Sikiric, P., Seiwerth, S., et al. (1997). Pentadecapeptide BPC 157 beneficially influences the healing of colon-colon anastomoses in rats, in: Cell Injury and Protection in the Gastrointestinal Tract. From basic sciences to clinical perspectives 1996, Mozsik, Gy., Nagy, L., Par, A. and Rainsford, K. D. (Eds), pp. 249–258. Kluwer Academic Publishers, Dordrecht.
  • 22. Sikiric, P., Seiwerth, S., Grabarevic, Z., et al. (1997). The effect of pentadecapeptide BPC 157, H2 blockers and sucralfate on new vessels and new granulation tissue formation, Gastroenterology 112,291.
  • 23. Sikiric, P., Jadrijevic, S., Seiwerth, S., et al. (1997). Pentadecapeptide BPC 157 reduces esophagojejunal anastomosis-esophageal ulceration in rats, Gastroenterology 112, 219.
  • 25. Bodis, B., Karadi, O., Nagy, L., et al. (1997). Evidence for direct cellular protective effect of PL-10 substances (synthesized parts of body protection compound BPC) and their specificity to gastric mucosal cells, Life Sci. 61, PL 243-PL 248.
  • 26. Veljaca, M., Pllana, R., Lesch, C. A., Sanchez, B., Chan, K. and Guglietta, A. (1994). Protective effect of BPC 157 on a rat model of colitis, Gastroenterology 106, 789.
  • 27. Veljaca, M., Lech, C. A., Pllana, R., Sanchez, B., Chan, K. and Guglietta, A. (1994). BPC-15 reduces trinitrobenzene sulfonic acid-induced colonic damage in rats, J. Pharmacol. Exp. Ther. 272,417–422.
  • 28. Veljaca, M, Chan, K. and Guglietta, A. (1995). Digestion of h-EGF, h-TGF α, and BPC 15 in human gastric juice, Gastroenterology 108, 761.
  • 29. Veljaca, M., Lesch, C. A., Sanchez, B., Low, J. and Guglietta, A. (1995). Protection of BPC-15 on TNBS-induced colitis in rats: possible mechanisms of action, Gastroenterology 108, 936.
  • 30. Bosnjak, Z. J., Graf, B. M. and Sikiric, P. (1994). Protective effects of newly isolated gastric peptide following hypoxic and reoxygenation injury in the isolated guinea pig heart, FASEB J. 8, A 129.
  • 31. Sandor, Z., Vincze, A. and Szabo, S. (1996). The protective effect of a recently isolated gastric peptide in acute and chronic gastroduodenal injury, FASEB J. 10, 171.
  • 32. Sandor, Z., Vincze, A., Jadus, M. R., et al. (1997). The protective effect of newly isolated peptide PL-10 in the iodoacetamide colitis model in rats, Gastroenterology 112, 400.
  • 33. Paré, W. and Kluczynski, J. M. (1994). The effect of new gastric juice peptide BPC on classic stress triad in stress procedure, Exp. Clin. Gastroenterol. 2, 234–236.
  • 34. Erceg, D., Simicevic, V. N., Kolega, M. and Dohoczky, C. (1997). Some aspects of PL-10.1.AK- 15 on the gastrointestinal tract, J. Physiol. (Paris) 91, 179–181.

Beneficial effect of BPC 157 on gastric lesions

This trial demonstrates the synergistic activity of BPC157 with certain neurons!

 

Digestive-Diseases-and-Sciences-JournalDigestive Diseases and Sciences Journal

August 1996, Volume 41, Issue 8, pp 1604-1614

Beneficial effect of a novel pentadecapeptide BPC 157 on gastric lesions induced by restraint stress, ethanol, indomethacin, and capsaicin neurotoxicity

 

Abstract
Very recently, the integrity of capsaicin somato sensory neurons and their protection were suggested to be related to the activity in nociception of a newly discovered 15-amino acid peptide, BPC 157, shown to have strong beneficial effect on intestinal and liver lesions.

Therefore, from this viewpoint, we have studied the gastroprotective effect of the pentadecapeptide BPC 157, on gastric lesions produced in rats by 96% ethanol, restraint stress, and indomethacin.

The possible involvement of sensory neurons in the salutary actions of BPC 157 (10µg/kg, 10 ng/kg intraperitoneally) was studied with capsaicin, which has differential effects on sensory neurons: a high dose in adult (125 mg/kg subcutaneously, 3 months old) or administration (50 mg/kg subcutaneously) to neonatal animals (age of the 7 days) destroys sensory fibers, whereas a low dose (500µg/kg intraperitoneally) activates neurotransmitter release and protective effects on the mucosa.

In the absence of capsaicin, BPC 157 protected gastric mucosa against ethanol, restraint, and indomethacin application. In the presence of neurotoxic doses of capsaicin, the negative influence of capsaicin on restraint, ethanol, or indomethacin lesions consistently affected salutary activity of BPC 157.

However, BPC 157 protection was still evident in the capsaicin-treated rats (either treated as adults or as newborns) in all of these assays. Interestingly, after neonatal capsaicin treatment, a complete abolition of BPC gastroprotection was noted if BPC 157 was applied as a single nanogram-regimen, but the mucosal protection was fully reversed when the same dose was used daily. In line with the excitatory dose of capsaicin the beneficial effectiveness of BPC 157 appears to be increased as well.

Taken together, these data provide evidence for complex synergistic interaction between the beneficial effectiveness of BPC 157 and peptidergic sensory afferent neuron activity.

 

Key words
pentadecapeptide BPC 157 organoprotective peptide gastric lesions capsaicin neurotoxicity rats gastroprotection neuroprotection

 

Source for this article: http://link.springer.com/article/10.1007%2FBF02087908

 

Useful Cited References:

  • 12. 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
  • 13. 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
  • 14. 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-aminoacid 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
  • 15. 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
  • 16. 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 duododenal 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
  • 18. 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
  • 19. 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
    20.
    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
  • 21. 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
  • 22. 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
  • 23. Veljaca M, Chan K, Guglietta A: Digestion of h-EGF, h-TGF alpha, and BPC-15 in human gastric juice. Gastroenterology 108:761, 1995
  • 48. Kalogjera L, Ries N, Baudoin T, Ferencic Z, Seiwerth S, Sikiric P: Dose dependent protective effect of BPC 157 in capasaicin induced rhinitis in rats. European Arch Otorhynolaringol 1996 (in press)