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

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概要

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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 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.

• 社団法人 日本薬理学会の論文
• 2008-09-20

著者

• Zoricic Ivan

  Department Of Pharmacology University Of Zagreb Medical School

• BLAGAIC Alenka

  Department of Pharmacology, Medical School, University of Zagreb

• RADIC Bozo

  Department of Pharmacology, Medical School, University of Zagreb

• ILIC Spomenko

  Department of Pharmacology, Medical School, University of Zagreb

• VUKSIC Tihomir

  Department of Pharmacology, Medical School, University of Zagreb

• ANIC Tomislav

  Department of Pharmacology, Medical School, University of Zagreb

• SIKIRIC Predrag

  Department of Pharmacology, Medical School, University of Zagreb

• BRCIC Luka

  Department of Pharmacology, Medical Faculty, University of Zagreb

• SEIWERTH Sven

  Department of Pharmacology, Medical Faculty, University of Zagreb

• Sever Marko

  Department Of Pharmacology University Of Zagreb Medical School

• Brcic Iva

  Institute Of Pathology University Of Zagreb Medical School

• Brcic Iva

  Department Of Pathology Zagreb University Hospital Center

• KLICEK Robert

  Department of Pharmacology, Medical School, University of Zagreb

• DRMIC Domagoj

  Department of Pharmacology, Medical School, University of Zagreb

• KOCMAN Ivan

  Department of Pharmacology, Medical School, University of Zagreb

• IVICA Mihovil

  Department of Pharmacology, Medical School, University of Zagreb

• BARISIC Ivan

  Department of Pharmacology, Medical School, University of Zagreb

• BERKOPIC Lidija

  Department of Pharmacology, Medical School, University of Zagreb

• VRCIC Hrvoje

  Department of Pharmacology, Medical School, University of Zagreb

• CORIC Marijana

  Department of Pathology, Medical School, University of Zagreb

• STANCIC ROKOTOV

  Department of Pharmacology, Medical School, University of Zagreb

• Radic Bozo

  Department Of Pharmacology University Of Zagreb Medical School

• Brcic Luka

  Institute Of Pathology University Of Zagreb Medical School

• Kocman Ivan

  Department Of Pharmacology Medical School University Of Zagreb

• Vrcic Hrvoje

  Department Of Pharmacology Medical School University Of Zagreb

• Anic Tomislav

  Department Of Pharmacology University Of Zagreb Medical School

• Klicek Robert

  Department Of Pharmacology Medical School University Of Zagreb

• Seiwerth Sven

  Institute Of Pathology University Of Zagreb Medical School

• Drmic Domagoj

  Department Of Pharmacology Medical School University Of Zagreb

• Ivica Mihovil

  Department Of Pharmacology Medical School University Of Zagreb

• Coric Marijana

  Department Of Pathology Medical School University Of Zagreb

• Blagaic Alenka

  Department Of Pharmacology Medical School University Of Zagreb

• Blagaic Alenka

  Departments Of Pharmacology And Pathology Medical Faculty University Of Zagreb

• Vuksic Tihomir

  Department Of Pharmacology Medical School University Of Zagreb

• Berkopic Lidija

  Department Of Pharmacology Medical School University Of Zagreb

• Stancic Rokotov

  Department Of Pharmacology Medical School University Of Zagreb

• Sikiric Predrag

  Department Of Pharmacology University Of Zagreb Medical School

• Ilic Spomenko

  Department Of Pharmacology Medical School University Of Zagreb

• Sever Marko

  Department Of Pharmacology Medical School University Of Zagreb

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• An Experimental Model of Prolonged Esophagitis With Sphincter Failure in the Rat and the Therapeutic Potential of Gastric Pentadecapeptide BPC 157
• 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
• Gastric Pentadecapeptide BPC 157 as an Effective Therapy for Muscle Crush Injury in the Rat
• Stable Gastric Pentadecapeptide BPC 157 in Trials for Inflammatory Bowel Disease (PL-10, PLD-116, PL14736, Pliva, Croatia) Heals Ileoileal Anastomosis in the Rat
• Doxorubicine-Congestive Heart Failure-Increased Big Endothelin-1 Plasma Concentration : Reversal by Amlodipine, Losartan, and Gastric Pentadecapeptide BPC157 in Rat and Mouse

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