Prolonged Esophagitis After Primary Dysfunction of the Pyloric Sphincter in the Rat and Therapeutic Potential of the Gastric Pentadecapeptide BPC 157

Abstract

Abstract. Seven or fourteen days or twelve months after suturing one tube into the pyloric sphincter (removed by peristalsis by the seventh day), rats exhibit prolonged esophagitis with a constantly lowered pressure not only in the pyloric, but also in the lower esophageal sphincter and a failure of both sphincters. Throughout the esophagitis experiment, gastric pentadecapeptide BPC 157 (PL 14736) is given intraperitoneally once a day (10 µg / kg, 10 ng / kg, last application 24 h before assessment), or continuously in drinking water at 0.16 µg / ml, 0.16 ng / ml (12 ml / rat per day), or directly into the stomach 5 min before pressure assessment (a water manometer connected to the drainage port of a Foley catheter implanted into the stomach either through an esophageal or duodenal incision). This treatment alleviates i) the esophagitis (macroscopically and microscopically, at either region or interval), ii) the pressure in the pyloric sphincter, and iii) the pressure in the lower esophageal sphincter (cmH 2 O). In the normal rats it increases lower esophageal sphincter pressure, but decreases the pyloric sphincter pressure. Ranitidine, given using the same protocol (50 mg / kg, intraperitoneally, once daily; 0.83 mg / ml in drinking water; 50 mg / kg directly into the stomach) does not have an effect in either rats with esophagitis or in normal rats.

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

“…Besides, the occurrence of myocytes contraction is essential for an appropriate wound closure (57). Possibly, the most recently demonstrated beneficial effects on injured muscle (6,7,12,13) and muscle healing of the striated (12) and smooth muscle (6,7,13) could also contribute to the fistula closing using BPC 157 application. Finally, it is effective without a carrier (2 -14, 17 -19, 27, 28, 31, 34 -36, 42 -46, 48 -52).…”

Gastric Pentadecapeptide BPC 157 and Short Bowel Syndrome in Rats

“…Throughout the whole experimental period in rats with short bowel we observed escalating short bowel syndrome with downhill course but recovery secondary to BPC 157 beneficial effect, weight gain (reaching the level characteristic of normal unoperated healthy rats), and generally Table 2 Jejunum diameter (mm, mean ± SD) following parenteral and peroral application of stable gastric pentadecapeptide BPC 157 in rats subjected to massive small bowel resection Mean ± SD Jejunum diameter (mm) in rats subjected to massive small bowel resection Experimental day These observations likely indicate the efficient and safe applicability of BPC 157 in trials for inflammatory bowel disease (PL14736, Pliva) [44,45], as an antiulcer peptide [17][18][19][20][21][22][23][24][25][26][27][28] efficient in wound (including muscle) [31][32][33][34][35][36][37][38][39][40][41][42][43] and intestinal anastomosis (note the increased anastomosis breaking strength in rats with short bowel treated with BPC 157), and fistula healing [1,2,29,30]. Supportingly, this pentadecapeptide was beneficial also after gastrectomy [22,23], and therefore effective after different massive resection.…”

“…Likewise, BPC 157 could particularly facilitate villus height and crypt depth adaptation in remaining small intestine. Besides the mentioned strong antiulcer potential [17][18][19][20][21][22][23][24][25][26][27][28] (most importantly, its antiulcer activity that parallels recovery of the AMP-ADP-ATP system in gastric mucosa [57] and increase in gastric mucosal blood flow at the ulcer margin [58]), this may be due to improved epithelization even in severely burned animals [32,33,37], diabetic [34] or immunocompromised [32,42] animals, and anastomotic and fistula healing [1,2,29,30]. Supportingly, its various wounds healing abilities [31][32][33][34][35][36][37][38][39][40][41][42][43] include also intestinal wounds [1,2,29,30], although visceral and skin wound healing were thought to be not comparable [63].…”

“…As an antiulcer peptide [17][18][19][20][21][22][23][24][25][26][27][28] it improved healing of intestinal anastomosis and fistula [1,2,28,29], skin [31][32][33][34][35][36][37], and other wounds [38][39][40][41][42][43], and was shown to be both efficient and safe in trials for inflammatory bowel disease (PL14736, Pliva) [44,45]. Likewise, it was found to be more effective both locally and systemically (perorally and parenterally) than standard treatments, e.g., as therapy for gastrointestinal tract ulcers [17,[20][21][22][23][24][25][26][27][28] and other wounds [32][33][34][35][36], intestinal anastomosis [1,2], and gastrocutaneous and colocutaneous fistula …”

“…Likewise, it was found to be more effective both locally and systemically (perorally and parenterally) than standard treatments, e.g., as therapy for gastrointestinal tract ulcers [17,[20][21][22][23][24][25][26][27][28] and other wounds [32][33][34][35][36], intestinal anastomosis [1,2], and gastrocutaneous and colocutaneous fistula [29,30]. An interesting aspect may be that it improves healing of muscle [38,39] observed after transection (quadriceps muscle) [38] or crushing (gastrocnemius complex) [39], and for sphincter function [20,21], and is commonly used without a carrier [1,2, unlike other peptides (for review see [46,47]). …”