S1823 Acute Pancreatitis Can Induce Esophagitis and Sphincter Failure as Well as Aggravate a Preexsisting Esophagitis and Sphincter Failure in Rats. Successful Effect of Stable Gastric Pentadecapeptide BPC 157 (PL 14736)

Abstract

Recently, we showed the failed sphincter function in esophagitis-rats (J Pharm Sci, 200, 2007) and that pyloric sphincter (PS) failure induced lower esophageal sphincter (LES) failure. The next focus was on whether acute pancreatitis can aggravate or even induce esophagitis development and/or affect the pressure in lower esophageal and pyloric sphincters. As a solution, we proposed an orally active, stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419, an anti-ulcer peptide efficient in trials for inflammatory bowel disease (PL 14736, Pliva) and various wound treatment, no toxicity reported). In esophagitis-rats with sphincter dysfunction (J Pharm Sci, 2006, 2007) BPC 157 attenuated esophagitis and recovered low pressure in LES and PS. Previously, it was concluded that it also attenuates acute pancreatitis (Dig Dis Sci, 1996). As we described before in rats (J Pharm Sci, 2007, Eur J Pharmacol, 1987, Dig Dis Sci, 1996), tube insertion into PS induced esophagitis and LES and PS failure while bile duct ligation induced acute pancreatitis, assessed at 24 hours after surgery. Fall or raise in sphincter pressure (cm H2O) was assessed as a percentage of initial values in normal rats. BPC 157 (10 µg, 10 ng/kg, i.p. or i.g.) was given immediately after surgery, and/or 5 min before sphincter pressure assessment. Acute pancreatitis+esophagitis vs. esophagitis-rats. Compared with esophagitis-rats (tube only into PS) (80% LES, 83% PS fall) acute pancreatitis in esophagitis-rats (bile duct ligation+tube into PS) additionally aggravated esophagitis and reduced LES- and PS-pressure to 71% (LES) and 70% (PS). Also, acute pancreatitis itself (bile duct ligation) induced esophagitis and reduced LES- and PS-pressure to 79% (LES) and 81% (PS). BPC 157 therapy macro/microscopically and biochemically attenuated esophagitis (tube into PS), acute pancreatitis +esophagitis (bile duct ligation+tube into PS) and acute pancreatitis (bile duct ligation) and generally induced an increase in pressure of LES and PS(110% LES, 105% PS raise in esophagitis-rats ; 105% LES, 102% PS raise in acute pancreatitis+esophagitis-rats ; 111% LES, 107% PS raise in acute pancreatitis-rats). Acute pancreatitis can induce esophagitis and sphincter failure as well as aggravate already existing esophagitis and sphincter failure in rats while BPC 157 can be a successful medication.