title: 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.
abstract: We focused on the therapeutic effect of the stable gastric pentadecapeptide BPC 157 and how its action is related to nitric oxide (NO) in persistent colocutaneous fistula in rats (at 5 cm from anus, colon defect of 5 mm, skin defect of 5 mm); this peptide has been shown to be safe in clinical trials for inflammatory bowel disease (PL14736) and safe for intestinal anstomosis therapy. BPC 157 (10 microg/kg, 10 ng/kg) was applied i) in drinking water until the animals were sacrificed at post-operative day 1, 3, 5, 7, 14, 21, and 28; or ii) once daily intraperitoneally (first application 30 min following surgery, last 24 h before sacrifice) alone or with N(G)-nitro-L-arginine methyl ester (L-NAME) (5 mg/kg), L-arginine (200 mg/kg), and their combinations. Sulphasalazine (50 mg/kg) and 6-alpha-methylprednisolone (1 mg/kg) were given once daily intraperitoneally. BPC 157 accelerated parenterally or perorally the healing of colonic and skin defect, leading to the suitable closure of the fistula, macro/microscopically, biomechanically, and functionally (larger water volume sustained without fistula leaking). L-NAME aggravated the healing failure of colocutaneous fistulas, skin, and colon wounds (L-NAME groups). L-Arginine was effective only with blunted NO generation (L-NAME + L-arginine groups) but not without (L-arginine groups). All of the BPC 157 beneficial effects remained unchanged with blunted NO-generation (L-NAME + BPC 157 groups) and with NO substrate (L-arginine + BPC 157 groups) as well as L-NAME and L-arginine co-administration (L-NAME + L-arginine + BPC 157 groups). Sulphasalazine was only moderately effective, and corticosteroid even had an aggravating effect.
authors.affiliation: Department of Pharmacology, Medical School, University of Zagreb, Croatia.
authors.forename: Robert
authors.initials: R
authors.lastname: Klicek
authors.forename: Marko
authors.initials: M
authors.lastname: Sever
authors.forename: Bozo
authors.initials: B
authors.lastname: Radic
authors.forename: Domagoj
authors.initials: D
authors.lastname: Drmic
authors.forename: Ivan
authors.initials: I
authors.lastname: Kocman
authors.forename: Ivan
authors.initials: I
authors.lastname: Zoricic
authors.forename: Tihomir
authors.initials: T
authors.lastname: Vuksic
authors.forename: Mihovil
authors.initials: M
authors.lastname: Ivica
authors.forename: Ivan
authors.initials: I
authors.lastname: Barisic
authors.forename: Spomenko
authors.initials: S
authors.lastname: Ilic
authors.forename: Lidija
authors.initials: L
authors.lastname: Berkopic
authors.forename: Hrvoje
authors.initials: H
authors.lastname: Vrcic
authors.forename: Luka
authors.initials: L
authors.lastname: Brcic
authors.forename: Alenka Boban
authors.initials: AB
authors.lastname: Blagaic
authors.forename: Marijana
authors.initials: M
authors.lastname: Coric
authors.forename: Iva
authors.initials: I
authors.lastname: Brcic
authors.forename: Dinko Stancic
authors.initials: DS
authors.lastname: Rokotov
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: D000758:Anesthesia; D000818:Animals; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D001120:Arginine / Q000494:pharmacology; D003108:Colonic Diseases / Q000188:drug therapy*; D017577:Cutaneous Fistula / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010446:Peptide Fragments / Q000627:therapeutic use*; D011506:Proteins / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000897:Anti-Ulcer Agents; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D011506:Proteins; D009569:Nitric Oxide; C083833:BPC 157; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester