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

  • Klicek Robert
    Department of Pharmacology, Medical School, University of Zagreb, Croatia
  • Sever Marko
    Department of Pharmacology, Medical School, University of Zagreb, Croatia
  • Radic Bozo
    Department of Pharmacology, Medical School, University of Zagreb, Croatia
  • Drmic Domagoj
    Department of Pharmacology, Medical School, University of Zagreb, Croatia
  • Kocman Ivan
    Department of Pharmacology, Medical School, University of Zagreb, Croatia
  • Zoricic Ivan
    Department of Pharmacology, Medical School, University of Zagreb, Croatia
  • Vuksic Tihomir
    Department of Pharmacology, Medical School, University of Zagreb, Croatia
  • Ivica Mihovil
    Department of Pharmacology, Medical School, University of Zagreb, Croatia
  • Barisic Ivan
    Department of Pharmacology, Medical School, University of Zagreb, Croatia
  • Ilic Spomenko
    Department of Pharmacology, Medical School, University of Zagreb, Croatia
  • Berkopic Lidija
    Department of Pharmacology, Medical School, University of Zagreb, Croatia
  • Vrcic Hrvoje
    Department of Pharmacology, Medical School, University of Zagreb, Croatia
  • Brcic Luka
    Department of Pathology, Medical School, University of Zagreb, Croatia
  • Blagaic Alenka Boban
    Department of Pharmacology, Medical School, University of Zagreb, Croatia
  • Coric Marijana
    Department of Pathology, Medical School, University of Zagreb, Croatia
  • Brcic Iva
    Department of Pathology, Medical School, University of Zagreb, Croatia
  • Rokotov Dinko Stancic
    Department of Pharmacology, Medical School, University of Zagreb, Croatia
  • Anic Tomislav
    Department of Pharmacology, Medical School, University of Zagreb, Croatia
  • Seiwerth Sven
    Department of Pathology, Medical School, University of Zagreb, Croatia
  • Sikiric Predrag
    Department of Pharmacology, Medical School, University of Zagreb, Croatia

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抄録

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 μg/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 NG-nitro-<sc>L</sc>-arginine methyl ester (<sc>L</sc>-NAME) (5 mg/kg), <sc>L</sc>-arginine (200 mg/kg), and their combinations. Sulphasalazine (50 mg/kg) and 6-α-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). <sc>L</sc>-NAME aggravated the healing failure of colocutaneous fistulas, skin, and colon wounds (<sc>L</sc>-NAME groups). <sc>L</sc>-Arginine was effective only with blunted NO generation (<sc>L</sc>-NAME + <sc>L</sc>-arginine groups) but not without (<sc>L</sc>-arginine groups). All of the BPC 157 beneficial effects remained unchanged with blunted NO-generation (<sc>L</sc>-NAME + BPC 157 groups) and with NO substrate (<sc>L</sc>-arginine + BPC 157 groups) as well as <sc>L</sc>-NAME and <sc>L</sc>-arginine co-administration (<sc>L</sc>-NAME + <sc>L</sc>-arginine + BPC 157 groups). Sulphasalazine was only moderately effective, and corticosteroid even had an aggravating effect.<br>

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