Stable gastric pentadecapeptide BPC 157 heals cysteamine-colitis and colon-colon-anastomosis and counteracts cuprizone brain injuries and motor disability

Journal of Physiology and Pharmacology

Volumn 64, Issue 5, 2013, Pages 597-612

  Klicek, R ^a   Kolenc, D ^a   Suran, J ^a   Drmic, D ^a   Brcic, L ^a   Aralica, G ^a   Sever, M ^a   Holjevac, J ^a   Radic, B ^a   Turudic, T ^a   Kokot, A ^a   Patrlj, L ^a   Rucman, R ^a   Seiwerth, S ^a   Sikiric, P ^a  

^a UNIVERSITY OF ZAGREB   (Croatia)

Author keywords

Anastomosis; Cerebellar ataxia; Colitis; Cuprizone; Cysteamine; Intestinal bowel disease; Stable gastric pentadecapeptide BPC 157

Indexed keywords

CUPRIZONE; GLYCYLGLUTAMYLPROLYLPROLYLPROLYLGLYCYLLYSYLPROLYLALANYLASPARTYLASPARTYLALANYLGLYCYLLEUCYLVALINE; MERCAPTAMINE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN DAMAGE; CEREBELLAR ATAXIA; COLITIS; COLON ANASTOMOSIS; CONTROLLED STUDY; CORPUS CALLOSUM; FORELIMB; MALE; MOTONEURON; MOTOR DYSFUNCTION; MULTIPLE SCLEROSIS; NONHUMAN; RAT; SPINAL CORD VENTRAL HORN; THALAMUS;

ANASTOMOSIS, SURGICAL; ANIMALS; ANTI-INFLAMMATORY AGENTS; ANTI-ULCER AGENTS; ATAXIA; BEHAVIOR, ANIMAL; BRAIN; BRAIN INJURIES; COLITIS, ULCERATIVE; COLON; CUPRIZONE; CYSTEAMINE; FORELIMB; INFLAMMATORY BOWEL DISEASES; MALE; MULTIPLE SCLEROSIS; NEUROPROTECTIVE AGENTS; PEPTIDE FRAGMENTS; PROTEINS; RATS; RATS, WISTAR;

EID: 84888211158     PISSN: 08675910     EISSN: 18991505     Source Type: Journal    
DOI: None     Document Type: Article

References (85)

1. Biesiada G, Czepiel J, Ptak-Belowska A, et al. Expression and release of leptin and proinflammatory cytokines in patients with ulcerative colitis and infectious diarrhea. J Physiol Pharmacol 2012; 63: 471-481.
2. Raithel M, Hagel AF, Zopf Y, et al. Analysis of immediate ex vivo release of nitric oxide from human colonic mucosa in gastrointestinally mediated allergy, inflammatory bowel disease and controls. J Physiol Pharmacol 2012; 63: 317-325.
3. Konturek PC, Brzozowski T, Konturek SJ. Stress and the gut: pathophysiology, clinical consequences, diagnostic approach and treatment options. J Physiol Pharmacol 2011; 62: 591-599.
4. Sikiric P, Seiwerth S, Rucman R, et al. Stable gastric pentadecapeptide BPC 157-NO-system relation. Curr Pharm Des 2013 Jun 10. [Epub ahead of print].
5. Sikiric P, Seiwerth S, Rucman R, et al. Toxicity by NSAIDs. Counteraction by stable gastric pentadecapeptide BPC 157. Curr Pharm Des 2013; 19: 76-83.
6. Sikiric P, Seiwerth S, Rucman R, et al. Stable gastric pentadecapeptide BPC 157: novel therapy in gastrointestinal tract. Curr Pharm Des 2011; 17: 1612-1632.
7. Sikiric P, Seiwerth S, Brcic L, et al. Revised Robert's cytoprotection and adaptive cytoprotection and stable gastric pentadecapeptide BPC 157. Possible significance and implications for novel mediator. Curr Pharm Des 2010; 16: 1224-1234.
8. Seiwerth S, Brcic L, Vuletic LB, et al. BPC 157 and blood vessels. Curr Pharm Des 2013 Jun 10. [Epub ahead of print].
9. Sikiric P, Seiwerth S, Rucman R, et al. Focus on ulcerative colitis: stable gastric pentadecapeptide BPC 157. Curr Med Chem 2012; 19: 126-132.
10. Sikiric P, Seiwerth S, Aralica G, et al. Therapy effect of antiulcer agents on new chronic cysteamine colon lesion in rat. J Physiol Paris 2001; 95: 283-288.
11. Sikiric P, Seiwerth S, Grabarevic Z, et al. Cysteamine-colon and cysteamine-duodenum lesions in rats. Attenuation by gastric pentadecapeptide BPC 157, cimetidine, ranitidine, atropine, omeprazole, sulphasalazine and methylprednisolone. J Physiol Paris 2001; 95: 261-270.
12. Kipp M, Clarner T, Dang J, Copray S, Beyer C. The cuprizone animal model: new insights into an old story. Acta Neuropathol 2009; 118: 723-736.
13. Thomas S, Baumgart DC. Targeting leukocyte migration and adhesion in Crohn's disease and ulcerative colitis. Inflammopharmacology 2012; 20: 1-18.
14. Danese S, Semeraro S, Marini M, et al. Adhesion molecules in inflammatory bowel disease: therapeutic implications for gut inflammation. Dig Liver Dis 2005; 37: 811-818.
15. 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.
16. Pevec D, Novinscak T, Brcic L, et al. Impact of pentadecapeptide BPC 157 on muscle healing impaired by systemic corticosteroid application. Med Sci Monit 2010; 16: 81-88.
17. 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.
18. Gjurasin M, Miklic P, Zupancic B, et al. Peptide therapy with pentadecapeptide BPC 157 in traumatic nerve injury. Regul Pept 2010; 160: 33-41.
19. Tudor M, Jandric I, Marovic A, et al. Traumatic brain injury in mice and pentadecapeptide BPC 157 effect. Regul Pept 2010; 160: 26-32.
20. Ilic S, Drmic D, Zarkovic K, et al. High hepatotoxic dose of paracetamol produces generalized convulsions and brain damage in rats. A counteraction with the stable gastric pentadecapeptide BPC 157 (PL 14736). J Physiol Pharmacol 2010; 61: 241-250.
21. Ilic S, Drmic D, Zarkovic K, et al. Ibuprofen hepatic encephalopathy, hepatomegaly, gastric lesion and gastric pentadecapeptide BPC 157 in rats. Eur J Pharmacol 2011; 667: 322-329.
22. Ilic S, Drmic D, Franjic S, et al. Pentadecapeptide BPC 157 and its effects on a NSAID toxicity model: diclofenac-induced gastrointestinal, liver, and encephalopathy lesions. Life Sci 2011; 88: 535-542.
23. Ilic S, Brcic I, Mester M, et al. 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. J Physiol Pharmacol 2009; 60(Suppl 7): 107-114.
24. Van Assche G, Lewis JD, Lichtenstein GR, et al. The London position statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn's and Colitis Organisation: safety. Am J Gastroenterol 2011; 106: 1594-1602.
25. Balenovic D, Bencic ML, Udovicic M, et al. Inhibition of methyldigoxin-induced arrhythmias by pentadecapeptide BPC 157: a relation with NO-system. Regul Pept 2009; 156: 83-89.
26. Barisic M, Balenovic D, Klicek R, et al. Mortal hyperkalemia disturbance in rats is NO-system related. The life saving effect of pentadecapeptide BPC 157. Regul Pept 2013; 181: 50-66.
27. Cesarec V, Becejac T, Misic M, et al. Pentadecapeptide BPC 157 and the esophagocutaneous fistula healing therapy. Eur J Pharmacol 2012; 701: 203-212.
28. Brcic L, Brcic I, Staresinic M, Novinscak T, Sikiric P, Seiwerth S. Modulatory effect of gastric pentadecapeptide BPC 157 on angiogenesis in muscle and tendon healing. J Physiol Pharmacol 2009; 60(Suppl. 7): 191-196.
29. Sikiric P, Separovic J, Anic T, et al. The effect of pentadecapeptide BPC 157, H2-blockers, omeprazole and sucralfate on new vessels and new granulation tissue formation. J Physiol Paris 1999; 93: 479-485.
30. Seiwerth S, Sikiric P, Grabarevic Z, et al. BPC 157's effect on healing. J Physiol Paris 1997; 91: 173-178.
31. 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.
32. Grabarevic Z, Tisljar M, Artukovic B, et al. The influence of BPC 157 on nitric oxide agonist and antagonist induced lesions in broiler chicks. J Physiol Paris 1997; 91: 139-149.
33. Lovric-Bencic M, Sikiric P, Hanzevacki JS, et al. Doxorubicine-congestive heart failure-increased big endothelin-1 plasma concentration: reversal by amlodipine, losartan, and gastric pentadecapeptide BPC 157 in rat and mouse. J Pharmacol Sci 2004; 95: 19-26.
34. Boban-Blagaic A, Blagaic V, Romic Z, et al. The influence of gastric pentadecapeptide BPC 157 on acute and chronic ethanol administration in mice. The effect of N(G)-nitro-L-arginine methyl ester and L-arginine. Med Sci Monit 2006; 12: 36-45.
35. Klicek R, Sever M, Radic B, et al. Pentadecapeptide BPC 157, in clinical trials as a therapy for inflammatory bowel disease (PL14736), is effective in the healing of colocutaneous fistulas in rats: role of the nitric oxide-system. J Pharmacol Sci 2008; 108: 7-17.
36. Cerovecki T, Bojanic I, Brcic L, et al. Pentadecapeptide BPC 157 (PL 14736) improves ligament healing in the rat. J Orthop Res 2010; 28: 1155-1161.
37. Staresinic M, Sebecic B, Patrlj L, et al. Gastric pentadecapeptide BPC 157 accelerates healing of transected rat Achilles tendon and in vitro stimulates tendocytes growth. J Orthop Res 2003; 21: 976-983.
38. 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.
39. Sikiric P, Seiwerth S, Grabarevic Z, et al. 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 promotors and gut peptides. Life Sci 1994; 54: 63-68.
40. Hrelec M, Klicek R, Brcic L, et al. Abdominal aorta anastomosis in rats and stable gastric pentadecapeptide BPC 157, prophylaxis and therapy. J Physiol Pharmacol 2009; 60(Suppl. 7): 161-165.
41. Stupnisek M, Franjic S, Drmic D, et al. Pentadecapeptide BPC 157 reduces bleeding time and thrombocytopenia after amputation in rats treated with heparin, warfarin or aspirin. Thromb Res 2012; 129: 652-659.
42. Vuksic T, Zoricic I, Brcic L, et al. Stable gastric pentadecapeptide BPC 157 in trials for inflammatory bowel disease (PL-10, PLD-116, PL14736, Pliva, Croatia) heals ileoileal anastomosis in the rat. Surg To d a y 2007; 37: 768-777.
43. Sever M, Klicek R, Radic B, et al. Gastric pentadecapeptide BPC 157 and short bowel syndrome in rats. Dig Dis Sci 2009; 54: 2070-2083.
44. 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: 212-221.
45. Bilic M, Bumber Z, Blagaic AB, Batelja L, Seiwerth S, Sikiric P. The stable gastric pentadecapeptide BPC 157, given locally, improves CO2 laser healing in mice. Burns 2005; 31: 310-315.
46. Mikus D, Sikiric P, Seiwerth S, et al. Pentadecapeptide BPC 157 cream improves burn-wound healing and attenuates burn-gastric lesions in mice. Burns 2001; 27: 817-827.
47. Krivic A, Anic T, Seiwerth S, Huljev D, Sikiric P. Achilles detachment in rat and stable gastric pentadecapeptide BPC 157: Promoted tendon-to-bone healing and opposed corticosteroid aggravation. J Orthop Res 2006; 24: 982-989.
48. Veljaca M, Lesch CA, Sanchez B, Low J, Guglietta A. Protection of BPC-15 on TNBS-induced colitis in rats: possiblemechanisms of action. Gastroenterology 1995; 108: 936.
49. Veljaca M, Lesch CA, Pllana R, Sanchez B, Chan K, Guglietta A. BPC-15 reduces trinitrobenzene sulfonic acid-inducedcolonic damage in rats. J Pharmacol Exp Ther 1994; 272: 417-422.
50. Orsolic N, Seiwerth S, Sikiric P. BPC 157 enhances function of immunological effector cells in mice. J Physiol Pharmacol 2009; 60(Suppl. 2): 69.
51. Bjarnason I, Hayllar J, MacPherson AJ, Russell AS. Side effects of nonsteroidal anti-inflammatory drugs on the small and large intestine in humans. Gastroenterology 1993; 104: 1832-1847.
52. Kaufmann HJ, Taubin HL. Nonsteroidal anti-inflammatory drugs activate quiescent inflammatory bowel disease. Ann Intern Med 1987; 107: 513-516.
53. Sikiric P, Seiwerth S, Grabarevic Z, et al. Pentadecapeptide BPC 157 positively affects both non-steroidal anti-inflammatory agent-induced gastrointestinal lesions and adjuvant arthritis in rats. J Physiol Paris 1997; 91: 113-122.
54. Subbaramaiah K, Yoshimatsu K, Scherl E, et al. Microsomal prostaglandin E synthase-1 is overexpressed in inflammatory bowel disease. Evidence for involvement of the transcription factor Egr-1. J Biol Chem 2004; 279: 12647-12658.
55. Howe CL, Mayoral S, Rodriguez M. Activated microglia stimulate transcriptional changes in primary oligodendrocytes via IL-1beta. Neurobiol Dis 2006; 23: 731-739.
56. Kouhsar SS, Karami M, Tafreshi AP, Roghani M, Nadoushan MR. Microinjection of l-arginine into corpus callosum cause reduction in myelin concentration and neuroinflammation. Brain Res 2011; 1392: 93-100.
57. O'Brien NC, Charlton B, Cowden WB, Willenborg DO. Nitric oxide plays a critical role in the recovery of Lewis rats from experimental autoimmune encephalomyelitis and the maintenance of resistance to reinduction. J Immunol 1999; 163: 6841-6847.
58. FitzGerald UF, Gilbey T, Brodie S, Barnett SC. Transcription factor expression and cellular redox in immature oligodendrocyte cell death: effect of Bcl-2. Mol Cell Neurosci 2003; 22: 516-529.
59. Sikiric P, Seiwerth S, Grabarevic Z, et al. Beneficial effect of a novel pentadecapeptide BPC 157 on gastric lesions induced by restraint stress, ethanol, indomethacin, and capsaicin neurotoxicity. Dig Dis Sci 1996; 41: 1604-1614.
60. Friese MA, Montalban X, Willcox N, Bell JI, Martin R, Fugger L. The value of animal models for drug development in multiple sclerosis. Brain 2006; 129: 1940-1952.
61. Tan YV, Waschek JA. Targeting VIP and PACAP receptor signalling: new therapeutic strategies in multiple sclerosis. ASN Neuro 2011; 3: e00065. doi: 10.1042/AN20110024.
62. Franco PG, Silvestroff L, Soto EF, Pasquini JM. Thyroid hormones promote differentiation of oligodendrocyte progenitor cells and improve remyelination after cuprizone-induced demyelination. Exp Neurol 2008; 212: 458-467.
63. Guyenet SJ, Furrer SA, Damian VM, Baughan TD, La Spada AR, Garden GA. A simple composite phenotype scoring system for evaluating mouse models of cerebellar ataxia. J Vis Exp 2010; 39: 1787.
64. Irvine KA, Ferguson AR, Mitchell KD, Beattie SB, Beattie MS, Bresnahan JC. A novel method for assessing proximal and distal forelimb function in the rat: the Irvine, Beatties and Bresnahan (IBB) forelimb scale. J Vis Exp 2010; 46: 2246.
65. Kim HJ, Miron VE, Dukala D, et al. Neurobiological effects of sphingosine 1-phosphate receptor modulation in the cuprizone model. FASEB J 2011; 25: 1509-1518.
66. Adamo AM, Paez PM, Escobar Cabrera E, et al. Remyelination after cuprizone-induced demyelination in the rat is stimulated by apotransferrin. Exp Neurol 2006; 198: 519-529.
67. Suzuki K, Kikkawa Y. Status spongiosus of CNS and hepatic changes induced by cuprizone (biscyclohexanone oxalyldihydrazone). Am J Pathol 1969; 54: 307-325.
68. Ludwin SK. Central nervous system demyelination and remyelination in the mouse: an ultrastructural study of cuprizone toxicity. Lab Invest 1978; 39: 597-612.
69. Matsushima GK, Morell P. The neurotoxicant, cuprizone, as a model to study demyelination and remyelination in the central nervous system. Brain Pathol 2001; 11: 107-116.
70. Blakemore WF. Remyelination of the superior cerebellar peduncle in old mice following demyelination induced by cuprizone. J Neurol Sci 1974; 22: 121-126.
71. Armstrong RC, Le TQ, Frost EE, Borke RC, Vana AC. Absence of fibroblast growth factor 2 promotes oligodendroglial repopulation of demyelinated white matter. J Neurosci 2002; 22: 8574-8585.
72. Wergeland S, Torkildsen O, Myhr KM, Mork SJ, Bo L. The cuprizone model: regional heterogeneity of pathology. APMIS 2012; 120: 648-657.
73. Xu H, Yang HJ, Rose GM, Li XM. Recovery of behavioral changes and compromised white matter in C57BL/6 mice exposed to cuprizone: effects of antipsychotic drugs. Front Behav Neurosci 2011; 5: 31.
74. Jelovac N, Sikiric P, Rucman R, et al. A novel pentadecapeptide, BPC 157, blocks the stereotypy produced acutely by amphetamine and the development of haloperidol-induced supersensitivity to amphetamine. Biol Psychiatry 1998; 43: 511-519.
75. Sikiric P, Marovic A, Matoz W, et al. A behavioural study of the effect of pentadecapeptide BPC 157 in Parkinson's disease models in mice and gastric lesions induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydrophyridine. J Physiol Paris 1999; 93: 505-512.
76. Sikiric P, Jelovac N, Jelovac-Gjeldum A, et al. Pentadecapeptide BPC 157 attenuates chronic amphetamine-induced behavior disturbances. Acta Pharmacol Sin 2002; 23: 412-422.
77. Jelovac N, Sikiric P, Rucman R, et al. Pentadecapeptide BPC 157 attenuates disturbances induced by neuroleptics: the effect on catalepsy and gastric ulcers in mice and rats. Eur J Pharmacol 1999; 379: 19-31.
78. Yuan XQ, Qiu G, Liu XJ, et al. Fluoxetine promotes remission in acute experimental autoimmune encephalomyelitis in rats. Neuroimmunomodulation 2012; 19: 201-208.
79. Taler M, Gil-Ad I, Korob I, Weizman A. The immunomodulatory effect of the antidepressant sertraline in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. Neuroimmunomodulation 2011; 18: 117-122.
80. Tohoyama Y, Sikiric P, Diksic M. Effects of pentadecapeptide BPC 157 on regional serotonin synthesis in the rat brain: alpha-methyl-L-tryptophan autoradiographic measurements. Life Sci 2004; 76: 345-357.
81. Boban Blagaic A, Blagaic V, Mirt M, et al. Gastric pentadecapeptide BPC 157 effective against serotonin syndrome in rats. Eur J Pharmacol 2005; 512: 173-179.
82. Jandric I, Vrcic H, Jandric Balen M, et al. Salutary effect of gastric pentadecapeptide BPC 157 in two different stress urinary incontinence models in female rats. Med Sci Monitor 2012; 19: 93-102.
83. Petrovic I, Dobric I, Drmic D, et al. BPC 157 therapy to detriment sphincters failure-esophagitis-pancreatitis in rat and acute pancreatitis patients low sphincters pressure. J Physiol Pharmacol 2011; 62: 527-534.
84. Dobric I, Drvis P, Petrovic I, et al. Prolonged esophagitis after primary dysfunction of the pyloric sphincter in the rat and therapeutic potential of the gastric pentadecapeptide BPC 157. J Pharmacol Sci 2007; 104: 7-18.
85. Petrovic I, Dobric I, Drvis P, et al. An experimental model of prolonged esophagitis with sphincter failure in the rat and the therapeutic potential of gastric pentadecapeptide BPC 157. J Pharmacol Sci 2006; 102: 269-277.