Tracheocutaneous Fistula Resolved by Pentadecapeptide BPC 157 Therapy Through the NO-System—Triple NO-Agent Approach in Rats

Madzarac, Goran; Becejac, Tomislav; Penovic, Toni; Drazenovic, Dominik; Kralj, Lucija; Popović Dolic, Marta; Sikiric, Suncana; Beketic Oreskovic, Lidija; Oreskovic, Ivana; Strbe, Sanja; Tubikanec, Ana Maria; Penavic, Mihovil; Vranes, Hrvoje; Krezic, Ivan; Kordic, Mario; Koprivanac, Antun; Vidovic, Tinka; Vlainić, Josipa; Stancic Rokotov, Dinko; Boban Blagaic, Alenka; Seiwerth, Sven; Skrtic, Anita; Sikiric, Predrag (2026) Tracheocutaneous Fistula Resolved by Pentadecapeptide BPC 157 Therapy Through the NO-System—Triple NO-Agent Approach in Rats. Pharmaceuticals, 19 (1). ISSN 1424-8247

PDF - Published Version - article Available under License Creative Commons Attribution. Download (3MB)

Abstract

Background/Objectives: This 7-day rat tracheocutaneous fistula study considered the not-studied issues of tracheocutaneous fistula course, wound healing, and fistula in the NO-system relations. Therefore, we focused on fistulas' severe course, tracheocutaneous fistula -> air leak -> compensatory diaphragmatic/abdominal "heaving", NO-system failed relations, and therapy resolution. Stable gastric pentadecapeptide BPC 157 was proposed. Methods: Tracheocutaneous fistula rats received daily medication (/kg), alone or combined, BPC 157 therapy (10 mu g, 10 ng, in drinking water or intraperitoneally) along with a triple NO-agent approach (L-NAME 5 mg, L-arginine 100 mg, and L-NAME+L-arginine, intraperitoneally). Results: Tracheocutaneous fistulas occurred as specific and NO-system-related as follows: NO system: blockade (L-NAME-aggravation) over-activity (L-arginine-amelioration) or immobilization (L-NAME+L-arginine oppose each other's effects). Controls presented severe clinical signs of respiratory distress, failed healing, skin and tracheal defects, a not-healed and open, macro/microscopically, and fistulous tract that was well-formed and wide, tracheal shrinking below the fistula, and clinically, open-mouth breathing, "heaving abdomen", cyanosis (bluish snout, ears, extremities), abundant secretion through the fistula, and weight loss. Fistula tissue NO level decreased, and the malondialdehyde (MDA) level increased. The BPC 157 therapy (both application routes) resulted in rapid recovery. Healing of defects (skin and trachea) and fistula closure, macro/microscopically, corresponded with clinical findings, avoiding observable clinical signs of dyspnea, reducing weight loss, and avoiding any sign of "heaving abdomen". BPC 157-treated rats displayed regular breathing movements without observable signs of respiratory distress. Finally, when combined, BPC 157 therapy upgrades L-arginine amelioration, abolishes L-NAME-induced worsening, and restores full healing after NO immobilization (L-NAME+L-arginine). BPC 157 counteracted increase in NO level and counteracted increase in MDA level. Conclusions: Thus, first, acting systemically, BPC 157 reverses tracheocutaneous fistula course in rats. It acts through the NO system.

Item Type:	Article
Uncontrolled Keywords:	BPC 157; L-NAME; L-NAME+L-arginine; L-arginine; rats; tracheocutaneous fistula
Subjects:	BIOMEDICINE AND HEALTHCARE
Divisions:	Division of Molecular Medicine
Depositing User:	Virna Brumnić
Date Deposited:	09 Apr 2026 10:21
URI:	http://fulir.irb.hr/id/eprint/11636
DOI:	10.3390/ph19010145

Actions (login required)

View Item