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Therapy for Unhealed Gastrocutaneous Fistulas in Rats as a Model for Analogous Healing of Persistent Skin Wounds and Persistent Gastric Ulcers: Stable Gastric Pentadecapeptide BPC 157, Atropine, Ranitidine, and Omeprazole.

Skorjanec S, Dolovski Z, Kocman I, Brcic L, Blagaic Boban A, Batelja L, Coric M, Sever M, Klicek R, Berkopic L, Radic B, Drmic D, Kolenc D, Ilic S, Cesarec V, Tonkic A, Zoricic I, Mise S, Staresinic M, Ivica M, Lovric Bencic M, Anic T, Seiwerth S, Sikiric P

Department of Pharmacology, Medical School, University of Zagreb, Salata 11, 10000, Zagreb, Croatia.

Objective This study focused on unhealed gastrocutaneous fistulas to resolve whether standard drugs that promote healing of gastric ulcers may simultaneously have the same effect on cutaneous wounds, and corticosteroid aggravation, and to demonstrate why peptides such as BPC 157 exhibit a greater healing effect. Therefore, with the fistulas therapy, we challenge the wound/growth factors theory of the analogous nonhealing of wounds and persistent gastric ulcers. Methods The healing rate of gastrocutaneous fistula in rat (2-mm-diameter stomach defect, 3-mm-diameter skin defect) validates macro/microscopically and biomechanically a direct skin wound/stomach ulcer relation, and identifies a potential therapy consisting of: (i) stable gastric pentadecapeptide BPC 157 [in drinking water (10 mug/kg) (12 ml/rat/day) or intraperitoneally (10 mug/kg, 10 ng/kg, 10 pg/kg)], (ii) atropine (10 mg/kg), ranitidine (50 mg/kg), and omeprazole (50 mg/kg), (iii) 6-alpha-methylprednisolone (1 mg/kg) [intraperitoneally, once daily, first application at 30 min following surgery; last 24 h before sacrifice (at postoperative days 1, 2, 3, 7, 14, and 21)]. Results Greater anti-ulcer potential and efficiency in wound healing compared with standard agents favor BPC 157, efficient in inflammatory bowel disease (PL-14736, Pliva), given in drinking water or intraperitoneally. Even after 6-alpha-methylprednisolone aggravation, BPC 157 promptly improves both skin and stomach mucosa healing, and closure of fistulas, with no leakage after up to 20 ml water intragastrically. Standard anti-ulcer agents, after a delay, improve firstly skin healing and then stomach mucosal healing, but not fistula leaking and bursting strength (except for atropine). Conclusion We conclude that BPC 157 may resolve analogous nonhealing of wounds and persistent gastric ulcers better than standard agents.

Published 23 July 2008 in Dig Dis Sci.
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