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Klicek, R; Sever, M; Radic, B; Drmic, D; Kocman, I; Zoricic, I; Vuksic, T; Ivica, M; Barisic, I; Ilic, S; Berkopic, L; Vrcic, H; Brcic, L; Blagaic, AB; Coric, M; Brcic, I; Rokotov, DS; Anic, T; Seiwerth, S; Sikiric, P.
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.
J Pharmacol Sci. 2008; 108(1): 7-17.
Doi: 10.1254/jphs.FP0072161
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- Co-authors Med Uni Graz
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Brcic Iva
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Brcic Luka
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- Abstract:
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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.
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Anesthesia -
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Animals -
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Anti-Ulcer Agents - therapeutic use
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Arginine - pharmacology
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Colonic Diseases - drug therapy
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Cutaneous Fistula - drug therapy
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Enzyme Inhibitors - pharmacology
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Inflammatory Bowel Diseases - drug therapy
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Male -
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NG-Nitroarginine Methyl Ester - pharmacology
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Nitric Oxide - biosynthesis Nitric Oxide - physiology
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Nitric Oxide Synthase - antagonists & inhibitors
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Peptide Fragments - therapeutic use
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Proteins - therapeutic use
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Rats -
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Rats, Wistar -
- Find related publications in this database (Keywords)
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stable gastric pentadecapeptide BPC 157
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colocutaneous fistula
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skin defect
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colon defect