Duodenocutaneous fistula in rats as a model for "wound healing-therapy" in ulcer healing: the effect of pentadecapeptide BPC 157, L-nitro-arginine methyl ester and L-arginine.
While very rarely reported, duodenocutanenous fistula research might alter the duodenal ulcer disease background and therapy. Our research focused on rat duodenocutaneous fistulas, therapy, stable gastric pentadecapeptide BPC 157, an anti-ulcer peptide that healed other fistulas, nitric oxide synthase-substrate L-arginine, and nitric oxide synthase-inhibitor L-nitro-arginine methyl ester (L-NAME). The hypothesis was, duodenal ulcer-healing, like the skin ulcer, using the successful BPC 157, with nitric oxide-system involvement, the "wound healing-therapy", to heal the duodenal ulcer, the fistula-model that recently highlighted gastric and skin ulcer healing. Pressure in the lower esophageal and pyloric sphincters was simultaneously assessed. Duodenocutaneous fistula-rats received BPC 157 (10 μg/kg or 10 ng/kg, intraperitoneally or perorally (in drinking water)), L-NAME (5 mg/kg intraperitoneally), L-arginine (100 mg/kg intraperitoneally) alone and/or together, throughout 21 days. Duodenocutaneous fistula-rats maintained persistent defects, continuous fistula leakage, sphincter failure, mortality rate at 40% until the 4(th) day, all fully counteracted in all BPC 157-rats. The BPC 157-rats experienced rapidly improved complete presentation (maximal volume instilled already at 7(th) day). L-NAME further aggravated the duodenocutaneous fistula-course (mortality at 70% until the 4(th) day); L-arginine was beneficial (no mortality; however, maximal volume instilled not before 21(st) day). L-NAME-worsening was counteracted to the control level with the L-arginine effect, and vice versa, while BPC 157 annulled the L-NAME effects (L-NAME + L-arginine; L-NAME + BPC 157; L-NAME + L-arginine + BPC 157 brought below the level of the control). It is likely that duodenocutaneous fistulas, duodenal/skin defect simultaneous healing, reinstated sphincter function, are a new nitric oxide-system related phenomenon. In conclusion, resolving the duodenocutanenous fistulashealing, nitric oxide-system involvement, should illustrate further wound healing therapy to heal duodenal ulcers.
Department of Pharmacology, Medical Faculty, University of Zagreb, Zagreb, Croatia.
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Skorjanec
Department of Anatomy and Neuroscience, Medical Faculty, J.J Strossmayer University of Osijek, Osijek, Croatia.
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Kokot
Department of Pharmacology, Medical Faculty, University of Zagreb, Zagreb, Croatia.
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Drmic
Department of Pharmacology, Medical Faculty, University of Zagreb, Zagreb, Croatia.
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Radic
Department of Pharmacology, Medical Faculty, University of Zagreb, Zagreb, Croatia.
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Sever
Department of Pharmacology, Medical Faculty, University of Zagreb, Zagreb, Croatia.
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Klicek
Department of Pathology, Medical Faculty, University of Zagreb, Zagreb, Croatia.
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Kolenc
Department of Pathology, Medical Faculty, University of Zagreb, Zagreb, Croatia.
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Zenko
Department of Pharmacology, Medical Faculty, University of Zagreb, Zagreb, Croatia.
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Lovric Bencic
Department of Pharmacology, Medical Faculty, University of Zagreb, Zagreb, Croatia.
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Belosic Halle
Department of Pharmacology, Medical Faculty, University of Zagreb, Zagreb, Croatia.
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Situm
Department of Pharmacology, Medical Faculty, University of Zagreb, Zagreb, Croatia.
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Zivanovic Posilovic
Department of Pharmacology, Medical Faculty, University of Zagreb, Zagreb, Croatia.
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Masnec
Department of Pharmacology, Medical Faculty, University of Zagreb, Zagreb, Croatia.
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Suran
Department of Pathology, Medical Faculty, University of Zagreb, Zagreb, Croatia.
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Aralica
Department of Pathology, Medical Faculty, University of Zagreb, Zagreb, Croatia.
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Seiwerth
Department of Pharmacology, Medical Faculty, University of Zagreb, Zagreb, Croatia. sikiric@mef.hr.
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Sikiric
D000818:Animals; D001120:Arginine / Q000627:therapeutic use*; D004378:Duodenal Diseases / Q000188:drug therapy* / Q000401:mortality; D004381:Duodenal Ulcer / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004386:Duodenum / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D049630:Esophageal Sphincter, Lower / Q000503:physiopathology; D005402:Fistula; D005769:Gastrointestinal Motility / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010446:Peptide Fragments / Q000627:therapeutic use*; D011506:Proteins / Q000627:therapeutic use*; D011706:Pyloric Antrum; D051381:Rats; D017208:Rats, Wistar; D012871:Skin Diseases / Q000188:drug therapy*; D014945:Wound Healing / Q000187:drug effects*
D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D011506:Proteins; C083833:BPC 157; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester