W1244 The Role of Adenine and Guanine in Beneficial Effects of the Gastric Pentadecapeptide BPC 157 (PL 14736) On Ileoileal Anastomosis Healing in Rats Impaired with Systemic Corticosteroid Application. Raman Spectroscopy Study

Commonly, the angiogenic growth factors signify healing. However, gastrointestinal ulceration is still poorly understood particularly with respect to a general pharmacological/pathophysiological role of various angiogenic growth factors implemented in growth factors wound healing concept. Thereby, we focused on the stable gastric pentadecapeptide BPC 157, a peptide given always alone vs. standard peptidergic angiogenic growth factors (EGF, FGF, VEGF), and numerous carriers. Further, we reviewed how the gastrointestinal tract healing could be generally perceived (i) in terms of angiogenic growth factors, and/or (ii) through the healing of extragastrointestinal tissues healing, such as tendon, ligament, muscle and bone, and vice versa. Respected were the beneficial effects obtained with free peptides or peptides with different carriers; EGF, FGF, VEGF, and BPC 157, their presentation along with injuries, and a healing commonality, providing their implementation in both gastrointestinal ulcer healing and tendon, ligament, muscle and bone healing. Only BPC 157 was consistently effective in all of the models of acute/chronic injury of esophagus, stomach, duodenum and lower gastrointestinal tract, intraperitoneally, per-orally or locally. Unlike bFGF-, EGF-, VEGF-gastrointestinal tract studies demonstrating improved healing, most of the studies on tendon, muscle and bone injuries provide evidence of their (increased) presentation along with the various procedures used to produce beneficial effects, compared to fewer studies in vitro, while in vivo healing has a limited number of studies, commonly limited to local application, diverse healing evidence with diverse carriers and delivery systems. Contrary to this, BPC 157 - using same regimens like in gastrointestinal healing studies - improves tendon, ligament and bone healing, accurately implementing its own angiogenic effect in the healing. Thus, we claim that just BPC 157 represents in practice a pharmacological and pathophysiological role of various peptidergic growth factors.

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The Healing of Colocutaneous Fistulas and Bile Duct Ligation. The Role of Pentadecapeptide BPC 157

Gastroenterology ◽

10.1016/s0016-5085(11)61882-9 ◽

2011 ◽

Vol 140 (5) ◽

pp. S-458

Author(s):

Andrej Ŝitum ◽

Robert Klicek ◽

Marina Barbaric ◽

Domagoj Drmic ◽

Alenka Boban Blagaic ◽

...

Keyword(s):

Bile Duct ◽

Bile Duct Ligation ◽

Bpc 157 ◽

Duct Ligation ◽

Pentadecapeptide Bpc 157

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Novel Cytoprotective Mediator, Stable Gastric Pentadecapeptide BPC 157. Vascular Recruitment and Gastrointestinal Tract Healing

Current Pharmaceutical Design ◽

10.2174/1381612824666180608101119 ◽

2018 ◽

Vol 24 (18) ◽

pp. 1990-2001 ◽

Cited By ~ 16

Author(s):

Predrag Sikiric ◽

Rudolf Rucman ◽

Branko Turkovic ◽

Marko Sever ◽

Robert Klicek ◽

...

Keyword(s):

Large Scale ◽

Venous Occlusion ◽

Cell Protection ◽

Caval Vein ◽

Bpc 157 ◽

Beneficial Effects ◽

Mucosal Integrity ◽

Inferior Caval Vein ◽

Cytoprotective Agent ◽

Pentadecapeptide Bpc 157

Years ago, we revealed a novel cytoprotective mediator, stable gastric pentadecapeptide BPC 157, particular anti-ulcer peptide that heals different organs lesions when given as a therapy, native in human gastric juice while maintaining GI-tract mucosal integrity, already tested in trials (ulcerative colitis and now multiple sclerosis). The stomach cytoprotection is the most fundamental concept, stomach cell protection and endothelium protection are largely elaborated, but so far cell, protection and endothelium protection outside of the stomach were not implemented in the therapy. However, having managed these two points, stomach cell protection and endothelium protection, either one or together, even much more than standard cytoprotective agents do, BPC 157 employed large scale of its beneficial effects seen in various organs. Providing endothelium protection, BPC 157 was shown to prevent formation and reverse established thrombosis in anastomosed abdominal aorta as well as venous thrombosis after inferior caval vein occlusion, and attenuate bleeding prolongation and thrombocytopenia after amputation, without or with anticoagulants, or venous occlusion, and finally counteract effect of L-NAME and/or L- arginine. Now, with BPC 157 application, we reveal the third most important part of the cytoprotection concept: with the stomach cell and endothelium protection to recover mucosal integrity, BPC 157 as prototype cytoprotective agent should also control blood vessel function, depending upon injury, perforated defect or vessel obstruction. After a perforated injury (i.e., stomach), BPC 157 therapy activates blood vessels “running” towards defect. After obstruction (i.e., inferior caval vein), BPC 157 activates vessels “running” towards bypassing defect, collaterals functioning. Reestablished blood flow, and largely reversed injurious course may practically implement the cytoprotection concept.

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Mo1249 The Healing of Colocutaneous Fistulas and Diclofenac Overdose. The Role of Pentadecapeptide BPC 157

Gastroenterology ◽

10.1016/s0016-5085(15)32194-6 ◽

2015 ◽

Vol 148 (4) ◽

pp. S-649-S-650

Author(s):

Robert Klicek ◽

Gorana Aralica ◽

Leonardo Patrlj ◽

Masa Hrelec Patrlj ◽

Predrag Pavic ◽

...

Keyword(s):

Bpc 157 ◽

Pentadecapeptide Bpc 157

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Fistulas Healing. Stable Gastric Pentadecapeptide BPC 157 Therapy

Current Pharmaceutical Design ◽

10.2174/1381612826666200424180139 ◽

2020 ◽

Vol 26 (25) ◽

pp. 2991-3000 ◽

Cited By ~ 1

Author(s):

Predrag Sikiric ◽

Domagoj Drmic ◽

Marko Sever ◽

Robert Klicek ◽

Alenka B. Blagaic ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gastrointestinal Tract ◽

Corneal Ulcer ◽

Bowel Resection ◽

Bpc 157 ◽

Beneficial Effects ◽

Duodenal Lesions ◽

Pentadecapeptide Bpc 157 ◽

Large Bowel Resection ◽

Entire Gastrointestinal Tract

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.

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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

Journal of Pharmacological Sciences ◽

10.1254/jphs.fp0072161 ◽

2008 ◽

Vol 108 (1) ◽

pp. 7-17 ◽

Cited By ~ 24

Author(s):

Robert Klicek ◽

Marko Sever ◽

Bozo Radic ◽

Domagoj Drmic ◽

Ivan Kocman ◽

...

Keyword(s):

Nitric Oxide ◽

Inflammatory Bowel Disease ◽

Clinical Trials ◽

Bowel Disease ◽

Oxide System ◽

Bpc 157 ◽

Pentadecapeptide Bpc 157 ◽

Inflammatory Bowel ◽

Nitric Oxide System

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Stable Gastric Pentadecapeptide BPC 157 Heals Established Vesicovaginal Fistula and Counteracts Stone Formation in Rats

Biomedicines ◽

10.3390/biomedicines9091206 ◽

2021 ◽

Vol 9 (9) ◽

pp. 1206

Author(s):

Domagoj Rasic ◽

Anita Zenko Sever ◽

Fran Rasic ◽

Sanja Strbe ◽

Zarko Rasic ◽

...

Keyword(s):

Drinking Water ◽

Functional Recovery ◽

Granulation Tissue ◽

Vesicovaginal Fistula ◽

Stone Formation ◽

Fistula Formation ◽

Minimal Volume ◽

Bpc 157 ◽

Beneficial Effects ◽

Pentadecapeptide Bpc 157

With the stable gastric pentadecapeptide BPC 157 therapy known to heal various both external and internal rat fistulas, we attempt to approach vesicovaginal fistula, continuous urine leaking through vagina, bladder stones, and a possible therapy solution among rats with well-formed 2 week-fistulas (vaginal/vesical 4 mm large defects) started with delayed therapy. Subsequent control fistula course (the subsequent 1, 2, 4, and 6 weeks) since beginning revealed the failed healing, fistula leaking, adhesions, urinary leaking through vagina, failed epithelization, collagenization, granulation tissue and neovascularization, increased inflammation, and necrosis. Thereby, the later intervals revealed the persistent inability to sustain even minimal volume, vesical, and vaginal defects and stone formation at the end of the experiment (fistula-time day 56). BPC 157 therapy (10 µg/kg, 10 ng/kg, intraperitoneally once time daily or perorally in drinking water until sacrifice) was initiated with a considerable delay (at 2 weeks after fistula formation). Already within 1 week therapy, all BPC 157 regimens stopped urinary leaking through vagina, reversed the otherwise resistant poor healing course to the increased epithelization, collagenization, granulation tissue and neovascularization, decreased inflammation, and decreased necrosis. Thereby, at later intervals, all BPC 157 rats exhibited a five times larger volume that can be sustained before leaking as in healthy, vesical, and vaginal defects completely closed and no stone formation. Thus, macro/microscopic and functional recovery, and counteracted stone formation. Concluding, BPC 157 therapy’s beneficial effects resulted in healing and no stone formation, with µg- and ng-regimens, either given daily perorally in drinking water or intraperitoneally.

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