The Effect of BPC 157 on Tracheocutaneous Fistula Healing in Rat

Abstract

IntroductionOne of the common late complications of a tracheotomy is tracheocutaneous fistula. The surgical procedure is needed to close such fistulas. BPC 157, anti‐ulcer peptide (GEPPPGKPADDAGLV, M.W. 1419) successful in trials for inflammatory bowel disease, wound treatment, effective alone without a carrier. BPC 157 interferes with NO‐system in vitro/in vivo on different models and different animal species. The impact of BPC 157 and NO‐system on gastrocutaneous, colocutaneous and oesophagocutaneous fistulas healing process indicates potential effect of BPC 157 in tracheocutaneous fistula healing process, which has not yet been investigated.MethodsAlbino Wistar male rats were used in this experiment, 220–280 g. Tracheocutaneous fistula, 4 mm trachea and skin defect, was surgically made under anaesthesia. Animals were treated according to the experiment protocol: a) drinking water p.o., b) BPC 157 (10 μg/kg, 12 ml/rat/day) p.o., c) BPC 157 (10 ng/kg, 12 ml/rat/day) p.o., d) saline 5ml/kg/day i.p., e) BPC 157 (10μg/kg, 5ml/kg/day) i.p., f) BPC 157 (10 ng/kg, 5 ml/kg/day) i.p., g) L‐NAME (5 mg/kg/day) i.p., h) L‐arginine (100 mg/kg/day) i.p., i) L‐NAME L‐arginine i.p., j) L‐NAME BPC 157 (μg) i.p., k) L‐arginine BPC 157 (μg) i.p., l) L‐NAME L‐arginine BPC 157 (μg) i.p., m) L‐NAME BPC 157 (ng) i.p., n) L‐arginine BPC 157 (ng) i.p., o) L‐NAME L‐arginine BPC 157 (ng) i.p.. Third, fifth and seventh postoperative day animals were euthanized. Fistula specimens were harvested and macroscopic and histological analysis was made.ResultsA consistent counteracting beneficial effect was shown in all animals treated with BPC 157, alone and with (L‐NAME) and/or L‐arginine in a 7‐day interval. BPC 157 accelerated healing of tracheocutaneous fistulas and showed macroscopic and histological healing improvements. Tracheocutaneous fistulas healing was improved speedily (BPC 157 completely counteracted L‐NAME effects (L‐NAME+BPC 157 and L‐NAME+L‐arginine+BPC 157 groups), or with delay and to less extent (L‐arginine) or aggravated, rapidly and prominently (L‐NAME). L‐arginine reduces aggravation by NOS‐blockade (L‐NAME) to the control levels. Also, BPC 157 more than nullifies the effect of L‐NAME.ConclusionBPC 157 improved healing of both tracheal and skin defects and mediated fistula closing. This effect was shared by L‐arginine, with an opposite effect seen by L‐NAME, thereby portraying NO‐system involvement in the healing of tracheocutaneous fistula.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.