An Experimental Model of Prolonged Esophagitis With Sphincter Failure in the Rat and the Therapeutic Potential of Gastric Pentadecapeptide BPC 157

Abstract

Abstract. We report a simple novel rat model that combines prolonged esophagitis and parallel sphincters failure. The anti-ulcer gastric pentadecapeptide BPC 157, which was found to be stable in gastric juice, and is being evaluated in inflammatory bowel disease trials, is an antiesophagitis therapy that recovers failed sphincters. Twelve or twenty months after the initial challenge (tubes sutured into sphincters for one week and then spontaneously removed by peristalsis), rats exhibit prolonged esophagitis (confluent hemorrhagic and yellowish lesions, thinner epithelium and superficial corneal layer, with stratification derangement); constantly lowered pressure of both sphincters (assessed by using a water manometer connected to the drainage port of a Foley catheter implanted into the stomach either through esophageal or duodenal incision); and both lower esophageal and pyloric sphincter failure. Throughout the esophagitis experiment, BPC 157 was given at either 10 µg / kg, i.p., once a day (last application 24 h before assessment) or alternatively, it was given continuously in drinking water at 0.16 µg/ ml (12 ml / rat). This treatment recovers i) esophagitis (macroscopically and microscopically, at either region or investigated time period) and ii) pressure in both sphincters (cmH 2 O). In addition, BPC 157 (10 µg / kg) or saline (1 ml / rat, 5 ml / kg) was specifically given directly into the stomach; pressure assessment was performed at 5 min thereafter. The effect of BPC 157 is specific because in normal rats, it increases lower esophageal sphincter-pressure, but decreases pyloric sphincter-pressure. Ranitidine, given as the standard drug using the same protocol (50 mg / kg, i.p., once daily; 0.83 mg / ml in drinking water; or 50 mg / kg directly into the stomach) had no effect.

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

“…The tubes were temporarily inserted into the sphincters, and they were naturally evacuated by peristalsis by the end of the first week (4). We have also reported the successful therapy with the pentadecapeptide BPC 157, but not ranitidine (4). This finding was not so surprising given the considerable healing potential of the gastric pentadecapeptide BPC 157 (5 -21).…”

“…The close relationship between interstitial cells of Cajal and nerve fibers within the tunica muscularis of gastrointestinal organs is critical for the lower esophageal sphincter and pylorus function (3). We have reported recently a rat model of prolonged esophagitis with complete sphincter failure (4). The tubes were temporarily inserted into the sphincters, and they were naturally evacuated by peristalsis by the end of the first week (4).…”

“…We have reported recently a rat model of prolonged esophagitis with complete sphincter failure (4). The tubes were temporarily inserted into the sphincters, and they were naturally evacuated by peristalsis by the end of the first week (4). We have also reported the successful therapy with the pentadecapeptide BPC 157, but not ranitidine (4).…”

“…We thought that it would be interesting to see, once the pyloric sphincter dysfunction is established, whether the pentadecapeptide BPC 157 effect on pyloric sphincter pressure could change the aggressive course of esophagitis. The gastric pentadecapeptide BPC 157 is a stable anti-ulcer peptide (4 -12), particularly in human gastric juice (13), and it is more effective than standard agents (4,5,8,11,12,16). It also protects the esophageal mucosa (4,11) and mediates salivary gland function (8).…”

“…The gastric pentadecapeptide BPC 157 is a stable anti-ulcer peptide (4 -12), particularly in human gastric juice (13), and it is more effective than standard agents (4,5,8,11,12,16). It also protects the esophageal mucosa (4,11) and mediates salivary gland function (8). Gastric pentadecapeptide BPC 157, coded PL-10, PLD-116, and PL 14736 by Pliva, Croatia, is in clinical trials for the therapy of inflammatory bowel disease (14) and wound healing (9,10,20,21), including muscle healing after complete transection (15), with no toxicity reported so far (14).…”