Tracheocutaneous Fistula Resolved by Pentadecapeptide BPC 157 Therapy Through the NO-System-Triple NO-Agent Approach in Rats.
This 7-day rat study investigated the course of surgically created tracheocutaneous fistulas and whether the pentadecapeptide BPC 157 could promote healing, with a focus on the nitric oxide (NO) system's role. Rats with tracheocutaneous fistulas displayed severe respiratory distress, including open-mouth breathing, abdominal "heaving," cyanosis, abundant fistula secretion, weight loss, failed skin and tracheal wound healing, a well-formed fistulous tract, and tracheal shrinking below the fistula site. Tissue analyses showed decreased NO levels and increased malondialdehyde (MDA), a marker of oxidative stress. BPC 157, administered either intraperitoneally or in drinking water, was reported by the authors to accelerate fistula closure, improve macro- and microscopic healing of skin and tracheal defects, reduce respiratory distress signs, and counteract the NO and MDA changes observed in untreated controls. Using a "triple NO-agent" approach (L-NAME to block NO synthesis, L-arginine to enhance it, or both combined), the study further reported that BPC 157 could override L-NAME-induced worsening, enhance L-arginine-induced improvement, and restore healing even under combined NO immobilization. Key limitations include the exclusive use of an animal model, small experimental groups typical of rat studies, and the absence of human data.
Why this grade: All experiments were conducted exclusively in rats; no human participants or clinical data were included, limiting direct translation of findings to human medicine.
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 µg, 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.
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