title: An experimental model of prolonged esophagitis with sphincter failure in the rat and the therapeutic potential of gastric pentadecapeptide BPC 157.
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 anti-esophagitis 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 micro g/kg, i.p., once a day (last application 24 h before assessment) or alternatively, it was given continuously in drinking water at 0.16 micro g/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 (cmH2O). In addition, BPC 157 (10 micro g/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.
authors.affiliation: Department of Pharmacology, Medical Faculty, University of Zagreb, Zagreb, Croatia.
authors.forename: Igor
authors.initials: I
authors.lastname: Petrovic
authors.forename: Ivan
authors.initials: I
authors.lastname: Dobric
authors.forename: Petar
authors.initials: P
authors.lastname: Drvis
authors.forename: Drazen
authors.initials: D
authors.lastname: Shejbal
authors.forename: Luka
authors.initials: L
authors.lastname: Brcic
authors.forename: Alenka Boban
authors.initials: AB
authors.lastname: Blagaic
authors.forename: Lovorka
authors.initials: L
authors.lastname: Batelja
authors.forename: Neven
authors.initials: N
authors.lastname: Kokic
authors.forename: Ante
authors.initials: A
authors.lastname: Tonkic
authors.forename: Stjepan
authors.initials: S
authors.lastname: Mise
authors.forename: Tomislav
authors.initials: T
authors.lastname: Baotic
authors.forename: Mario
authors.initials: M
authors.lastname: Staresinic
authors.forename: Bozo
authors.initials: B
authors.lastname: Radic
authors.forename: Ana
authors.initials: A
authors.lastname: Jakir
authors.forename: Tihomir
authors.initials: T
authors.lastname: Vuksic
authors.forename: Tomislav
authors.initials: T
authors.lastname: Anic
authors.forename: Sven
authors.initials: S
authors.lastname: Seiwerth
authors.forename: Predrag
authors.initials: P
authors.lastname: Sikiric
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D049630:Esophageal Sphincter, Lower / Q000503:physiopathology*; D004941:Esophagitis / Q000503:physiopathology*; D005260:Female; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D010446:Peptide Fragments / Q000627:therapeutic use*; D011312:Pressure; D011506:Proteins / Q000627:therapeutic use*; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000503:physiopathology
chemical_list: D000897:Anti-Ulcer Agents; D006635:Histamine H2 Antagonists; D010446:Peptide Fragments; D011506:Proteins; D011899:Ranitidine; C083833:BPC 157