Fistulas Healing. Stable Gastric Pentadecapeptide BPC 157 Therapy

Author(s): Predrag Sikiric*, Domagoj Drmic, Marko Sever, Robert Klicek, Alenka B. Blagaic, Ante Tvrdeic, Tamara Kralj, Katarina K. Kovac, Jaksa Vukojevic, Marko Siroglavic, Slaven Gojkovic, Ivan Krezic, Katarina H. Pavlov, Domagoj Rasic, Ivan Mirkovic, Antonio Kokot, Anita Skrtic, Sven Seiwerth

Journal Name: Current Pharmaceutical Design

Volume 26 , Issue 25 , 2020


Become EABM
Become Reviewer
Call for Editor

Abstract:

This review is focused on the healing of fistulas and stable gastric pentadecapeptide BPC 157. Assuming that the healing of the various wounds is essential also for the gastrointestinal fistulas healing, the healing effect on fistulas in rats, consistently noted with the stable gastric pentadecapeptide BPC 157, may raise several interesting possibilities. BPC 157 is originally an anti-ulcer agent, native to and stable in human gastric juice (for more than 24 h). Likely, it is a novel mediator of Robert’s cytoprotection maintaining gastrointestinal mucosal integrity. Namely, it is effective in the whole gastrointestinal tract, and heals various wounds (i.e., skin, muscle, tendon, ligament, bone; ulcers in the entire gastrointestinal tract; corneal ulcer); LD1 is not achieved. It is used in ulcerative colitis clinical trials, and now in multiple sclerosis, and addressed in several reviews. Therefore, it is not surprising that BPC 157 has documented consistent healing of the various gastrointestinal fistulas, external (esophagocutaneous, gastrocutaneous, duodenocutaneous, colocutaneous) and internal (colovesical, rectovaginal). Taking fistulas as a pathological connection, this rescue is verified with the beneficial effects in rats with the various gastrointestinal anastomoses, esophagogastric, jejunoileal, colo-colonic, ileoileal, esophagojejunal, esophagoduodenal, and gastrojejunal. This beneficial effect occurs equally when the gastrointestinal anastomoses are impaired with the application of NSAIDs, cysteamine, large bowel resection, as well as concomitant esophageal, gastric, and duodenal lesions and/or ulcerative colitis presentation, short bowel syndrome progression, liver and brain disturbances presentation. Particular aspects of the BPC 157 healing of the fistulas are especially emphasized.

Keywords: Stable gastric pentadecapeptide BPC 157, fistulas healing, therapy, esophagoduodenal, colovesical, rectovaginal.

[1]
Tonolini M, Magistrelli P. Enterocutaneous fistulas: a primer for radiologists with emphasis on CT and MRI. Insights Imaging 2017; 8(6): 537-48.
[http://dx.doi.org/10.1007/s13244-017-0572-3] [PMID: 28963700]
[2]
Orangio GR. Enterocutaneous fistula: medical and surgical management including patients with Crohn’s disease. Clin Colon Rectal Surg 2010; 23(3): 169-75.
[http://dx.doi.org/10.1055/s-0030-1262984] [PMID: 21886466]
[3]
Visschers RG, van Gemert WG, Winkens B, Soeters PB, Olde Damink SW. Guided treatment improves outcome of patients with enterocutaneous fistulas. World J Surg 2012; 36(10): 2341-8.
[http://dx.doi.org/10.1007/s00268-012-1663-4] [PMID: 22669399]
[4]
Sikiric P, Hahm KB, Boban Blagaic A, et al. Stable gastric pentadecapeptide BPC 157, Robert’s stomach cytoprotection/adaptive cytoprotection/organoprotection, Selye’s stress coping response: progress, achievement, future. Gut Liver 2019.
[PMID: 31158953]
[5]
Seiwerth S, Rucman R, Turkovic B, et al. BPC 157 and Standard Angiogenic Growth Factors. Gastrointestinal Tract Healing, Lessons from Tendon, Ligament, Muscle and Bone Healing. Curr Pharm Des 2018; 24(18): 1972-89.
[http://dx.doi.org/10.2174/1381612824666180712110447] [PMID: 29998800]
[6]
Kang EA, Han YM, An JM, et al. BPC157 as Potential Agent Rescuing from Cancer Cachexia. Curr Pharm Des 2018; 24(18): 1947-56.
[http://dx.doi.org/10.2174/1381612824666180614082950] [PMID: 29898649]
[7]
Sikiric P, Rucman R, Turkovic B, et al. Novel Cytoprotective Mediator, Stable Gastric Pentadecapeptide BPC 157. Vascular Recruitment and Gastrointestinal Tract Healing. Curr Pharm Des 2018; 24(18): 1990-2001.
[http://dx.doi.org/10.2174/1381612824666180608101119] [PMID: 29879879]
[8]
Sikiric P, Seiwerth S, Rucman R, et al. Stress in Gastrointestinal Tract and Stable Gastric Pentadecapeptide BPC 157. Finally, do we have a Solution? Curr Pharm Des 2017; 23(27): 4012-28.
[http://dx.doi.org/10.2174/1381612823666170220163219] [PMID: 28228068]
[9]
Sikiric P, Seiwerth S, Rucman R, et al. Brain-gut axis and pentadecapeptide BPC 157: Theoretical and practical implications. Curr Neuropharmacol 2016; 14(8): 857-65.
[http://dx.doi.org/10.2174/1570159X13666160502153022] [PMID: 27138887]
[10]
Seiwerth S, Brcic L, Vuletic LB, et al. BPC 157 and blood vessels. Curr Pharm Des 2014; 20(7): 1121-5.
[http://dx.doi.org/10.2174/13816128113199990421] [PMID: 23782145]
[11]
Sikiric P, Seiwerth S, Rucman R, et al. Stable gastric pentadecapeptide BPC 157-NO-system relation. Curr Pharm Des 2014; 20(7): 1126-35.
[http://dx.doi.org/10.2174/13816128113190990411] [PMID: 23755725]
[12]
Sikiric P, Seiwerth S, Rucman R, et al. Toxicity by NSAIDs. Counteraction by stable gastric pentadecapeptide BPC 157. Curr Pharm Des 2013; 19(1): 76-83.
[PMID: 22950504]
[13]
Sikiric P, Seiwerth S, Rucman R, et al. Focus on ulcerative colitis: stable gastric pentadecapeptide BPC 157. Curr Med Chem 2012; 19(1): 126-32.
[http://dx.doi.org/10.2174/092986712803414015] [PMID: 22300085]
[14]
Sikiric P, Seiwerth S, Rucman R, et al. Stable gastric pentadecapeptide BPC 157: novel therapy in gastrointestinal tract. Curr Pharm Des 2011; 17(16): 1612-32.
[http://dx.doi.org/10.2174/138161211796196954] [PMID: 21548867]
[15]
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(10): 1224-34.
[http://dx.doi.org/10.2174/138161210790945977] [PMID: 20166993]
[16]
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(5-6): 214-21.
[http://dx.doi.org/10.1007/s10787-006-1531-7] [PMID: 17186181]
[17]
Sikirić 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(5): 313-27.
[http://dx.doi.org/10.1016/0928-4257(93)90038-U] [PMID: 8298609]
[18]
Skorjanec S, Dolovski Z, Kocman I, et al. Therapy for unhealed gastrocutaneous fistulas in rats as a model for analogous healing of persistent skin wounds and persistent gastric ulcers: stable gastric pentadecapeptide BPC 157, atropine, ranitidine, and omeprazole. Dig Dis Sci 2009; 54(1): 46-56.
[http://dx.doi.org/10.1007/s10620-008-0332-9] [PMID: 18649140]
[19]
Cesarec V, Becejac T, Misic M, et al. Pentadecapeptide BPC 157 and the esophagocutaneous fistula healing therapy. Eur J Pharmacol 2013; 701(1-3): 203-12.
[http://dx.doi.org/10.1016/j.ejphar.2012.11.055] [PMID: 23220707]
[20]
Skorjanec S, Kokot A, Drmic D, et al. Duodenocutaneous fistula in rats as a model for “wound healing-therapy” in ulcer healing: the effect of pentadecapeptide BPC 157, L-nitro-arginine methyl ester and L-arginine. J Physiol Pharmacol 2015; 66(4): 581-90.
[PMID: 26348082]
[21]
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(1): 7-17.
[http://dx.doi.org/10.1254/jphs.FP0072161] [PMID: 18818478]
[22]
Grgic T, Grgic D, Drmic D, et al. Stable gastric pentadecapeptide BPC 157 heals rat colovesical fistula. Eur J Pharmacol 2016; 780: 1-7.
[http://dx.doi.org/10.1016/j.ejphar.2016.02.038] [PMID: 26875638]
[23]
Baric M, Sever AZ, Vuletic LB, et al. Stable gastric pentadecapeptide BPC 157 heals rectovaginal fistula in rats. Life Sci 2016; 148: 63-70.
[http://dx.doi.org/10.1016/j.lfs.2016.02.029] [PMID: 26872976]
[24]
Seiwerth S, Sikiric P, Grabarevic Z, et al. BPC 157's effect on healing. J Physiol Paris 1997; 91(3-5): 173-8.
[http://dx.doi.org/10.1016/S0928-4257(97)89480-6] [PMID: 9403790]
[25]
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(8): 817-27.
[http://dx.doi.org/10.1016/S0305-4179(01)00055-9] [PMID: 11718984]
[26]
Sikiric P, Seiwerth S, Mise S, et al. Corticosteroid-impairment of healing and gastric pentadecapeptide BPC-157 creams in burned mice. Burns 2003; 29(4): 323-34.
[http://dx.doi.org/10.1016/S0305-4179(03)00004-4] [PMID: 12781609]
[27]
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(3): 310-5.
[http://dx.doi.org/10.1016/j.burns.2004.10.013] [PMID: 15774286]
[28]
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(5): 1109-17.
[http://dx.doi.org/10.1002/jor.20089] [PMID: 16609979]
[29]
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(3): BR81-8.
[PMID: 20190676]
[30]
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(8): 716-25.
[http://dx.doi.org/10.1007/s00595-007-3706-2] [PMID: 18668315]
[31]
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): 191-6.
[PMID: 20388964]
[32]
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(6): 976-83.
[http://dx.doi.org/10.1016/S0736-0266(03)00110-4] [PMID: 14554208]
[33]
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(5): 982-9.
[http://dx.doi.org/10.1002/jor.20096] [PMID: 16583442]
[34]
Krivic A, Majerovic M, Jelic I, Seiwerth S, Sikiric P. Modulation of early functional recovery of Achilles tendon to bone unit after transection by BPC 157 and methylprednisolone. Inflamm Res 2008; 57(5): 205-10.
[http://dx.doi.org/10.1007/s00011-007-7056-8] [PMID: 18594781]
[35]
Cerovecki T, Bojanic I, Brcic L, et al. Pentadecapeptide BPC 157 (PL 14736) improves ligament healing in the rat. J Orthop Res 2010; 28(9): 1155-61.
[http://dx.doi.org/10.1002/jor.21107] [PMID: 20225319]
[36]
Sebecić B, Nikolić V, Sikirić P, et al. 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 1999; 24(3): 195-202.
[http://dx.doi.org/10.1016/S8756-3282(98)00180-X] [PMID: 10071911]
[37]
Drmic D, Kolenc D, Ilic S, et al. Celecoxib-induced gastrointestinal, liver and brain lesions in rats, counteraction by BPC 157 or L-arginine, aggravation by L-NAME. World J Gastroenterol 2017; 23(29): 5304-12.
[http://dx.doi.org/10.3748/wjg.v23.i29.5304] [PMID: 28839430]
[38]
Drmic D, Samara M, Vidovic T, et al. Counteraction of perforated cecum lesions in rats: Effects of pentadecapeptide BPC 157, L-NAME and L-arginine. World J Gastroenterol 2018; 24(48): 5462-76.
[http://dx.doi.org/10.3748/wjg.v24.i48.5462] [PMID: 30622376]
[39]
Amic F, Drmic D, Bilic Z, et al. Bypassing major venous occlusion and duodenal lesions in rats, and therapy with the stable gastric pentadecapeptide BPC 157, L-NAME and L-arginine. World J Gastroenterol 2018; 24(47): 5366-78.
[http://dx.doi.org/10.3748/wjg.v24.i47.5366] [PMID: 30598581]
[40]
Djakovic Z, Djakovic I, Cesarec V, et al. Esophagogastric anastomosis in rats: Improved healing by BPC 157 and L-arginine, aggravated by L-NAME. World J Gastroenterol 2016; 22(41): 9127-40.
[http://dx.doi.org/10.3748/wjg.v22.i41.9127] [PMID: 27895400]
[41]
Lojo N, Rasic Z, Zenko Sever A, et al. Effects of diclofenac, L-NAME, L-arginine, and pentadecapeptide BPC 157 on gastrointestinal, liver, and brain lesions, failed anastomosis, and intestinal adaptation deterioration in 24 hour-short-bowel rats. PLoS One 2016; 11(9): e0162590
[http://dx.doi.org/10.1371/journal.pone.0162590] [PMID: 27627764]
[42]
Klicek R, Kolenc D, Suran J, et al. Stable gastric pentadecapeptide BPC 157 heals cysteamine-colitis and colon-colon-anastomosis and counteracts cuprizone brain injuries and motor disability. J Physiol Pharmacol 2013; 64(5): 597-612.
[PMID: 24304574]
[43]
Sever M, Klicek R, Radic B, et al. Gastric pentadecapeptide BPC 157 and short bowel syndrome in rats. Dig Dis Sci 2009; 54(10): 2070-83.
[http://dx.doi.org/10.1007/s10620-008-0598-y] [PMID: 19093208]
[44]
Masnec S, Kokot A, Zlatar M, et al. Perforating corneal injury in rat and pentadecapeptide BPC 157. Exp Eye Res 2015; 136: 9-15.
[http://dx.doi.org/10.1016/j.exer.2015.04.016] [PMID: 25912999]
[45]
Robert A. Cytoprotection by prostaglandins. Gastroenterology 1979; 77(4 Pt 1): 761-7.
[http://dx.doi.org/10.1016/0016-5085(79)90235-X] [PMID: 38173]
[46]
Robert A. Cytoprotection and prostaglandins. Klin Wochenschr 1986; 64(Suppl. 7): 40-3.
[PMID: 3560780]
[47]
Robert A, Nezamis JE, Lancaster C, Davis JP, Field SO, Hanchar AJ. Mild irritants prevent gastric necrosis through “adaptive cytoprotection” mediated by prostaglandins. Am J Physiol 1983; 245(1): G113-21.
[PMID: 6869543]
[48]
Robert A, Nezamis JE, Lancaster C, Hanchar AJ. Cytoprotection by prostaglandins in rats. Prevention of gastric necrosis produced by alcohol, HCl, NaOH, hypertonic NaCl, and thermal injury. Gastroenterology 1979; 77(3): 433-43.
[http://dx.doi.org/10.1016/0016-5085(79)90002-7] [PMID: 456839]
[49]
Lancaster C, Robert A. Intestinal lesions produced by prednisolone: prevention (cytoprotection) by 16,16-dimethyl prostaglandin E2. Am J Physiol 1978; 235(6): E703-8.
[PMID: 736130]
[50]
Szabo S, Usadel KH. Cytoprotection - organoprotection by somatostatin: gastric and hepatic lesions. Experientia 1982; 38(2): 254-6.
[http://dx.doi.org/10.1007/BF01945097] [PMID: 6120852]
[51]
Robert A, Lum JT, Lancaster C, Olafsson AS, Kolbasa KP, Nezamis JE. Prevention by prostaglandins of caerulein-induced pancreatitis in rats. Lab Invest 1989; 60(5): 677-91.
[PMID: 2469859]
[52]
Szabó S. Critical and timely review of the concept of gastric cytoprotection. Acta Physiol Hung 1989; 73(2-3): 115-27.
[PMID: 2688357]
[53]
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(6): 479-85.
[http://dx.doi.org/10.1016/S0928-4257(99)00123-0] [PMID: 10672992]
[54]
Hsieh MJ, Liu HT, Wang CN, et al. Therapeutic potential of pro-angiogenic BPC157 is associated with VEGFR2 activation and up-regulation. J Mol Med (Berl) 2017; 95(3): 323-33.
[http://dx.doi.org/10.1007/s00109-016-1488-y] [PMID: 27847966]
[55]
Huang T, Zhang K, Sun L, et al. Body protective compound-157 enhances alkali-burn wound healing in vivo and promotes proliferation, migration, and angiogenesis in vitro. Drug Des Devel Ther 2015; 9: 2485-99.
[http://dx.doi.org/10.2147/DDDT.S82030] [PMID: 25995620]
[56]
Chang CH, Tsai WC, Hsu YH, Pang JH. Pentadecapeptide BPC 157 enhances the growth hormone receptor expression in tendon fibroblasts. Molecules 2014; 19(11): 19066-77.
[http://dx.doi.org/10.3390/molecules191119066] [PMID: 25415472]
[57]
Chang CH, Tsai WC, Lin MS, Hsu YH, Pang JH. 2011.
[58]
Tkalcević VI, Cuzić 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): 212-21.
[http://dx.doi.org/10.1016/j.ejphar.2007.05.072] [PMID: 17628536]
[59]
Vukojević J, Siroglavić M, Kašnik K, et al. Rat inferior caval vein (ICV) ligature and particular new insights with the stable gastric pentadecapeptide BPC 157. Vascul Pharmacol 2018; 106: 54-66.
[http://dx.doi.org/10.1016/j.vph.2018.02.010] [PMID: 29510201]
[60]
Lazić R, Gabrić N, Dekaris I, Bosnar D, Boban-Blagaić A, Sikirić P. Gastric pentadecapeptide BPC 157 promotes corneal epithelial defects healing in rats. Coll Antropol 2005; 29(1): 321-5.
[PMID: 16117343]
[61]
Keremi B, Lohinai Z, Komora P, et al. Antiinflammatory effect of BPC 157 on experimental periodontitis in rats. J Physiol Pharmacol 2009; 60(Suppl. 7): 115-22.
[PMID: 20388954]
[62]
Gamulin Serec K, Bilic V, Balarin M, et al. Monitoring the healing process of rat bones usin Raman spectroscopy. J Mol Struct 2013; 1044: 308-13.
[http://dx.doi.org/10.1016/j.molstruc.2013.01.049]
[63]
Radeljak S, Seiwerth S, Sikiric P. BPC 157 inhibits cell growth and VEGF signalling via the MAPK kinase pathway in the human melanoma cell line. Melanoma Res 2004; 14: A14-5.
[http://dx.doi.org/10.1097/00008390-200408000-00050]
[64]
Kniery KR, Johnson EK, Steele SR. Operative considerations for rectovaginal fistulas. World J Gastrointest Surg 2015; 7(8): 133-7.
[http://dx.doi.org/10.4240/wjgs.v7.i8.133] [PMID: 26328032]
[65]
Aungst MJ, Fischer JR, Bonhage MR, Albright TS, Noel KA, Wright J. Rectovaginal fistula model in the New Zealand white rabbit. Int Urogynecol J Pelvic Floor Dysfunct 2010; 21(7): 885-8.
[http://dx.doi.org/10.1007/s00192-010-1118-0] [PMID: 20186389]
[66]
Aungst MJ, Bearss JJ, Lewis BS, Fischer JR, Bonhage MR, Wright J Jr. Interposition grafts for rectovaginal fistula repair in the New Zealand white rabbit. Int Urogynecol J Pelvic Floor Dysfunct 2010; 21(6): 737-42.
[http://dx.doi.org/10.1007/s00192-010-1096-2] [PMID: 20143048]
[67]
Roshanravan R, Ghahramani L, Hosseinzadeh M, et al. A new method to repair recto-vaginal fistula: Use of human amniotic membrane in an animal model. Adv Biomed Res 2014; 3: 114.
[http://dx.doi.org/10.4103/2277-9175.131033] [PMID: 24804188]
[68]
Rivadeneira DE, Ruffo B, Amrani S, Salinas C. Rectovaginal fistulas: current surgical management. Clin Colon Rectal Surg 2007; 20(2): 96-101.
[http://dx.doi.org/10.1055/s-2007-977487] [PMID: 20011383]
[69]
Becejac T, Cesarec V, Drmic D, et al. An endogeous defensive concept, renewed cytoprotection/adaptive cytoprotection: intra(per)-oral/intragastric strong alcohol in rat. Involvement of pentadecapeptide BPC 157 and nitric oxide system. J Physiol Pharmacol 2018; 69(3): 429-40.
[PMID: 30279308]
[70]
Vitaic S, Stupnisek M, Drmic D, et al. Nonsteroidal anti-inflammatory drugs-induced failure of lower esophageal and pyloric sphincter and counteraction of sphincters failure with stable gatric pentadecapeptide BPC 157 in rats. J Physiol Pharmacol 2017; 68(2): 265-72.
[PMID: 28614776]
[71]
Belosic Halle Z, Vlainic J, Drmic D, et al. Class side effects: decreased pressure in the lower oesophageal and the pyloric sphincters after the administration of dopamine antagonists, neuroleptics, anti-emetics, L-NAME, pentadecapeptide BPC 157 and L-arginine. Inflammopharmacology 2017; 25(5): 511-22.
[http://dx.doi.org/10.1007/s10787-017-0358-8] [PMID: 28516373]
[72]
Barisic I, Balenovic D, Klicek R, et al. Mortal hyperkalemia disturbances in rats are NO-system related. The life saving effect of pentadecapeptide BPC 157. Regul Pept 2013; 181: 50-66.
[http://dx.doi.org/10.1016/j.regpep.2012.12.007] [PMID: 23327997]
[73]
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(5): 527-34.
[PMID: 22204800]
[74]
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(1): 7-18.
[http://dx.doi.org/10.1254/jphs.FP0061322] [PMID: 17452811]
[75]
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(3): 269-77.
[http://dx.doi.org/10.1254/jphs.FP0060070] [PMID: 17116974]
[76]
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 Monit Basic Res 2013; 19: 93-102.
[http://dx.doi.org/10.12659/MSMBR.883828] [PMID: 23478678]
[77]
Kokot A, Zlatar M, Stupnisek M, et al. NO system dependence of atropine-induced mydriasis and L-NAME- and L-arginine-induced miosis: Reversal by the pentadecapeptide BPC 157 in rats and guinea pigs. Eur J Pharmacol 2016; 771: 211-9.
[http://dx.doi.org/10.1016/j.ejphar.2015.12.016] [PMID: 26698393]
[78]
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 Today 2007; 37(9): 768-77.
[http://dx.doi.org/10.1007/s00595-006-3498-9] [PMID: 17713731]
[79]
Sikiric P, Jadrijevic S, Seiwerth S, et al. Long-lasting cytoprotection after pentadecapeptide BPC 157, ranitidine, sucralfate or cholestyramine application in reflux oesophagitis in rats. J Physiol Paris 1999; 93(6): 467-77.
[http://dx.doi.org/10.1016/S0928-4257(99)00124-2] [PMID: 10672991]
[80]
Sikirić P, Mikus D, Seiwerth S, et al. Pentadecapeptide BPC 157, cimetidine, ranitidine, bromocriptine, and atropine effect in cysteamine lesions in totally gastrectromized rats: a model for cytoprotective studies. Dig Dis Sci 1997; 42(5): 1029-37.
[http://dx.doi.org/10.1023/A:1018893220943] [PMID: 9149058]
[81]
Sikirić P, Seiwerth S, Desković S, et al. New model of cytoprotection/adaptive cytoprotection in rats: endogenous small irritants, antiulcer agents and indomethacin. Eur J Pharmacol 1999; 364(1): 23-31.
[http://dx.doi.org/10.1016/S0014-2999(98)00818-8] [PMID: 9920181]
[82]
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): 161-5.
[PMID: 20388960]
[83]
Gjurasin M, Miklic P, Zupancic B, et al. Peptide therapy with pentadecapeptide BPC 157 in traumatic nerve injury. Regul Pept 2010; 160(1-3): 33-41.
[http://dx.doi.org/10.1016/j.regpep.2009.11.005] [PMID: 19903499]
[84]
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(5): 652-9.
[http://dx.doi.org/10.1016/j.thromres.2011.07.035] [PMID: 21840572]
[85]
Stupnisek M, Kokot A, Drmic D, et al. Pentadecapeptide BPC 157 Reduces Bleeding and Thrombocytopenia after Amputation in Rats Treated with Heparin, Warfarin, L-NAME and L-Arginine. PLoS One 2015; 10(4): e0123454
[http://dx.doi.org/10.1371/journal.pone.0123454] [PMID: 25897838]
[86]
Luetic K, Sucic M, Vlainic J, et al. Cyclophosphamide induced stomach and duodenal lesions as a NO-system disturbance in rats: L-NAME, L-arginine, stable gastric pentadecapeptide BPC 157. Inflammopharmacology 2017; 25(2): 255-64.
[http://dx.doi.org/10.1007/s10787-017-0330-7] [PMID: 28255738]
[87]
Duzel A, Vlainic J, Antunovic M, et al. Stable gastric pentadecapeptide BPC 157 in the treatment of colitis and ischemia and reperfusion in rats: New insights. World J Gastroenterol 2017; 23(48): 8465-88.
[http://dx.doi.org/10.3748/wjg.v23.i48.8465] [PMID: 29358856]
[88]
Sever AZ, Sever M, Vidovic T, et al. Stable gastric pentadecapeptide BPC 157 in the therapy of the rats with bile duct ligation. Eur J Pharmacol 2019; 847: 130-42.
[http://dx.doi.org/10.1016/j.ejphar.2019.01.030] [PMID: 30690000]
[89]
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 BPC157 in rat and mouse. J Pharmacol Sci 2004; 95(1): 19-26.
[http://dx.doi.org/10.1254/jphs.95.19] [PMID: 15153646]
[90]
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(1-3): 83-9.
[http://dx.doi.org/10.1016/j.regpep.2009.05.008] [PMID: 19465062]
[91]
Strinic D, Belosic Halle Z, Luetic K, et al. BPC 157 counteracts QTc prolongation induced by haloperidol, fluphenazine, clozapine, olanzapine, quetiapine, sulpiride, and metoclopramide in rats. Life Sci 2017; 186: 66-79.
[http://dx.doi.org/10.1016/j.lfs.2017.08.006] [PMID: 28797793]
[92]
Zivanovic-Posilovic G, Balenovic D, Barisic I, et al. Stable gastric pentadecapeptide BPC 157 and bupivacaine. Eur J Pharmacol 2016; 793: 56-65.
[http://dx.doi.org/10.1016/j.ejphar.2016.10.035] [PMID: 27815173]
[93]
Stambolija V, Stambolija TP, Holjevac JK, et al. BPC 157: The counteraction of succinylcholine, hyperkalemia, and arrhythmias. Eur J Pharmacol 2016; 781: 83-91.
[http://dx.doi.org/10.1016/j.ejphar.2016.04.004] [PMID: 27060013]
[94]
Balenovic D, Barisic I, Prkacin I, et al. Mortal furosemide-hypokalemia-disturbances in rats NO-system related. Shorten survival by L-NAME. Therapy benefit with BPC 157 peptide more than with L-arginine. J Clin Exp Cardiolog 2012; 3: 7.
[http://dx.doi.org/10.4172/2155-9880.1000201]
[95]
Tudor M, Jandric I, Marovic A, et al. Traumatic brain injury in mice and pentadecapeptide BPC 157 effect. Regul Pept 2010; 160(1-3): 26-32.
[http://dx.doi.org/10.1016/j.regpep.2009.11.012] [PMID: 19931318]
[96]
Tohyama Y, Sikirić P, Diksic M. Effects of pentadecapeptide BPC157 on regional serotonin synthesis in the rat brain: alpha-methyl-L-tryptophan autoradiographic measurements. Life Sci 2004; 76(3): 345-57.
[http://dx.doi.org/10.1016/j.lfs.2004.08.010] [PMID: 15531385]
[97]
Blagaic AB, Blagaic V, Romic Z, Sikiric P. The influence of gastric pentadecapeptide BPC 157 on acute and chronic ethanol administration in mice. Eur J Pharmacol 2004; 499(3): 285-90.
[http://dx.doi.org/10.1016/j.ejphar.2004.07.112] [PMID: 15381050]
[98]
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(1): 19-31.
[http://dx.doi.org/10.1016/S0014-2999(99)00486-0] [PMID: 10499368]
[99]
Jelovac N, Sikirić 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(7): 511-9.
[http://dx.doi.org/10.1016/S0006-3223(97)00277-1] [PMID: 9547930]
[100]
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(11-12): 535-42.
[http://dx.doi.org/10.1016/j.lfs.2011.01.015] [PMID: 21295044]
[101]
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(1-3): 322-9.
[http://dx.doi.org/10.1016/j.ejphar.2011.05.038] [PMID: 21645505]
[102]
Prkacin I, Aralica G, Perovic D, et al. Chronic cytoprotection: pentadecapeptide BPC 157, ranitidine and propranolol prevent, attenuate and reverse the gastric lesions appearance in chronic alcohol drinking rats. J Physiol Paris 2001; 95(1-6): 295-301.
[http://dx.doi.org/10.1016/S0928-4257(01)00041-9] [PMID: 11595453]
[103]
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(5): PL63-8.
[http://dx.doi.org/10.1016/0024-3205(94)00796-9] [PMID: 7904712]
[104]
Prkacin I, Separovic J, Aralicia G, et al. Portal hypertension and liver lesions in chronically alcohol drinking rats prevented and reversed by stable gastric pentadecapeptide BPC 157 (PL-10, PLD-116), and propranolol, but not ranitidine. J Physiol Paris 2001; 95(1-6): 315-24.
[http://dx.doi.org/10.1016/S0928-4257(01)00044-4] [PMID: 11595456]
[105]
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(2): 241-50.
[PMID: 20436226]
[106]
Sikirić P, Mazul B, Seiwerth S, et al. Pentadecapeptide BPC 157 interactions with adrenergic and dopaminergic systems in mucosal protection in stress. Dig Dis Sci 1997; 42(3): 661-71.
[http://dx.doi.org/10.1023/A:1018880000644] [PMID: 9073154]
[107]
Sikirić P, Seiwerth S, Grabarević 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(7): 1518-26.
[http://dx.doi.org/10.1007/BF02088582] [PMID: 8689934]
[108]
Sikiric P, Seiwerth S, Grabarevic Z, et al. 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 1993; 53(18): PL291-6.
[http://dx.doi.org/10.1016/0024-3205(93)90589-U] [PMID: 7901724]
[109]
Xue XC, Wu YJ, Gao MT, et al. Protective effects of pentadecapeptide BPC 157 on gastric ulcer in rats. World J Gastroenterol 2004; 10(7): 1032-6.
[http://dx.doi.org/10.3748/wjg.v10.i7.1032] [PMID: 15052688]
[110]
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): 107-14.
[PMID: 20388953]
[111]
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(1-6): 283-8.
[http://dx.doi.org/10.1016/S0928-4257(01)00039-0] [PMID: 11595451]
[112]
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(1-6): 261-70.
[http://dx.doi.org/10.1016/S0928-4257(01)00036-5] [PMID: 11595448]
[113]
Tlak Gajger I, Ribarić J, Smodiš Škerl M, Vlainić J, Sikirić P. Stable gastric pentadecapeptide BPC 157 in honeybee (Apis mellifera) therapy, to control Nosema ceranae invasions in apiary conditions. J Vet Pharmacol Ther 2018; 41(4): 614-21.
[http://dx.doi.org/10.1111/jvp.12509] [PMID: 29682749]
[114]
Grabarevic Z, Tisljar M, Artukovic B, et al. The influence of BPC 157 on nitric oxide agonist and antagonist induced lesions in broiler chicken. J Physiol Paris 1997; 91(3-5): 139-49.
[http://dx.doi.org/10.1016/S0928-4257(97)89478-8] [PMID: 9403788]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 26
ISSUE: 25
Year: 2020
Published on: 04 August, 2020
Page: [2991 - 3000]
Pages: 10
DOI: 10.2174/1381612826666200424180139
Price: $65

Article Metrics

PDF: 19
HTML: 3