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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- Klicek Robert
- Department of Pharmacology, Medical School, University of Zagreb, Croatia
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- Sever Marko
- Department of Pharmacology, Medical School, University of Zagreb, Croatia
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- Radic Bozo
- Department of Pharmacology, Medical School, University of Zagreb, Croatia
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- Drmic Domagoj
- Department of Pharmacology, Medical School, University of Zagreb, Croatia
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- Kocman Ivan
- Department of Pharmacology, Medical School, University of Zagreb, Croatia
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- Zoricic Ivan
- Department of Pharmacology, Medical School, University of Zagreb, Croatia
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- Vuksic Tihomir
- Department of Pharmacology, Medical School, University of Zagreb, Croatia
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- Ivica Mihovil
- Department of Pharmacology, Medical School, University of Zagreb, Croatia
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- Barisic Ivan
- Department of Pharmacology, Medical School, University of Zagreb, Croatia
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- Ilic Spomenko
- Department of Pharmacology, Medical School, University of Zagreb, Croatia
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- Berkopic Lidija
- Department of Pharmacology, Medical School, University of Zagreb, Croatia
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- Vrcic Hrvoje
- Department of Pharmacology, Medical School, University of Zagreb, Croatia
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- Brcic Luka
- Department of Pathology, Medical School, University of Zagreb, Croatia
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- Blagaic Alenka Boban
- Department of Pharmacology, Medical School, University of Zagreb, Croatia
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- Coric Marijana
- Department of Pathology, Medical School, University of Zagreb, Croatia
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- Brcic Iva
- Department of Pathology, Medical School, University of Zagreb, Croatia
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- Rokotov Dinko Stancic
- Department of Pharmacology, Medical School, University of Zagreb, Croatia
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- Anic Tomislav
- Department of Pharmacology, Medical School, University of Zagreb, Croatia
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- Seiwerth Sven
- Department of Pathology, Medical School, University of Zagreb, Croatia
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- 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>
収録刊行物
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- Journal of Pharmacological Sciences
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Journal of Pharmacological Sciences 108 (1), 7-17, 2008
公益社団法人 日本薬理学会
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詳細情報 詳細情報について
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- CRID
- 1390001205180487808
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- NII論文ID
- 10024322179
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- NII書誌ID
- AA11806667
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- ISSN
- 13478648
- 13478613
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- NDL書誌ID
- 9651802
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可