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

被引:50
作者
Klicek, Robert [1 ]
Sever, Marko [1 ]
Radic, Bozo [1 ]
Drmic, Domagoj [1 ]
Kocman, Ivan [1 ]
Zoricic, Ivan [1 ]
Vuksic, Tihornir [1 ]
Ivica, Mihovil [1 ]
Barisic, Ivan [1 ]
Ilic, Spomenko [1 ]
Berkopic, Lidija [1 ]
Vrcic, Hrvoje [1 ]
Brcic, Luka [2 ]
Blagaic, Alenka Boban [1 ]
Coric, Marijana [2 ]
Brcic, Iva [2 ]
Rokotov, Dinko Stancic [1 ]
Anic, Tomislav [1 ]
Seiwerth, Sven [2 ]
Sikiric, Predrag [1 ]
机构
[1] Univ Zagreb, Sch Med, Dept Pharmacol, Zagreb 10000, Croatia
[2] Univ Zagreb, Sch Med, Dept Pathol, Zagreb 10000, Croatia
关键词
stable gastric pentadecapeptide BPC 157; colocutaneous fistula; skin defect; colon defect;
D O I
10.1254/jphs.FP0072161
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 mu g/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.
引用
收藏
页码:7 / 17
页数:11
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