title: Pentadecapeptide BPC 157 and the esophagocutaneous fistula healing therapy.
abstract: Esophagocutaneous fistulas are a failure of the NO-system, due to NO-synthase blockage by the NOS-blocker L-NAME consequently counteracted by l-arginine and gastric pentadecapeptide BPC 157 (l-arginine <BPC 157), precipitating a therapeutic benefit. Previously, there was an established BPC 157-NO-system interaction. BPC 157 GEPPPGKPADDAGLV, MW 1419 (LD1 not achieved), is a safe and stable anti-ulcer peptide, successful in inflammatory bowel disease trials, counteracting esophagitis, sphincter failure, gastrointestinal and skin ulcers, gastrocutaneous or colocutaneous fistulas. We treated rats with established cervical esophagocutaneous fistulas throughout four days (both open skin and esophageal defects, with significant leakage) with BPC 157 (parenterally and perorally) and L-NAME (blocking NO genesis) and l-arginine (NO-substrate) alone or in combination. RT-PCR investigated eNOS, iNOS, COX-2 mRNA levels in the fistulas. We evidenced a closely inter-related process of unhealed skin, esophageal defects, unhealed fistulas (up regulated eNOS, iNOS and COX2 mRNA levels), usually lethal, particularly NO-system related and therapy dependent. Generally, the course of fistula healing was accelerated either to a greater extent (with BPC 157 (in particular, less eNOS gene expression) completely counteracting L-NAME effects, in L-NAME+BPC 157 and L-NAME+l-arginine+BPC 157 groups), or to a lesser extent (with l-arginine). Conversely, the process was aggravated, rapidly and prominently (with L-NAME). In particular, BPC 157 was effective either given per-orally/intraperitoneally, in μg- and ng-regimens. Shortly, defects started to heal, with less fistula leakage and no mortality at day 4. Failure of pyloric and lower esophageal sphincter pressure was restored, with practically no esophagitis.
authors.affiliation: Department of Pharmacology, University of Zagreb, Zagreb, Croatia.
authors.forename: Vedran
authors.initials: V
authors.lastname: Cesarec
authors.forename: Tomislav
authors.initials: T
authors.lastname: Becejac
authors.forename: Marija
authors.initials: M
authors.lastname: Misic
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Djakovic
authors.forename: Danijela
authors.initials: D
authors.lastname: Olujic
authors.forename: Domagoj
authors.initials: D
authors.lastname: Drmic
authors.forename: Luka
authors.initials: L
authors.lastname: Brcic
authors.forename: Dinko Stancic
authors.initials: DS
authors.lastname: Rokotov
authors.forename: Sven
authors.initials: S
authors.lastname: Seiwerth
authors.forename: Predrag
authors.initials: P
authors.lastname: Sikiric
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology; D017577:Cutaneous Fistula / Q000188:drug therapy* / Q000503:physiopathology*; D004347:Drug Interactions; D004935:Esophageal Diseases / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D011506:Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D010446:Peptide Fragments; D011506:Proteins; C083833:BPC 157; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester