Novel Approach in Therapy of Internal Fistulas: The Stable Gastric Pentadecapeptide BPC 157 in Therapy of Vesicovaginal Fistulas in Rats

Abstract

AimAs a novel approach in therapy of various fistulas, we hypothesize the stable gastric pentadecapeptide BPC 157 in therapy of internal fistulas, in particular vesicovaginal fistulas in rats. BPC 157 was originally an anti‐ulcer peptide used in trials for ulcerative colitis and now is in trials for the treatment of multiple sclerosis that largely interacts with NO‐system (Curr Pharm Des 2014;20(7):1126–35) and thought to be novel mediator of Robert's cytoprotection in rat studies, known to exert an immediate endothelium protection alongside with mucosal protection in stomach, known to counteract variously induced gastrointestinal lesions in various species, and in particular, various fistulas healing, external fistulas (esophagocutaneous (Eur J Pharmacol 2013;701(1–3):203–12), gastrocutaneous (Dig Dis Sci 2009;54(1):46–56), duodenocutaneous (J Physiol Pharmacol. 2015;66(4):581–90), colocutaneous (J Pharmacol Sci 2008;108(1):7–17)), and internal fistulas (colovesical (Eur J Pharmacol 2016;780:1–7) and rectovaginal (Life Sci 2016;148:63–70)). Thereby, providing simultaneous healing of different tissues, and likely correlation with human fistulas disturbances, it seems to be suited for the necessary generalization of the fistulas concept healing. Thus, BPC 157 was used in further therapy of internal fistulas, in particular vesicovaginal fistulas in rats.Materials and methodsIn female Wistar Albino rats, 200g vesicovaginal fistulas were created by longitudinal incision on the posterior wall of the urinary bladder and anterior vaginal wall (4mm) were performed. Fistula was created using single‐layer suture technique. Medication includes pentadecapeptide BPC 157 (10μg/kg/day, 10ng/kg/day) dissolved in saline, applied (a) intraperitoneally (first application 30min after surgery, last 24h before sacrifice, 5ml/kg) or (b) in drinking water (0.16μg/ml, 0.16ng/ml, 12ml/rat/day) or an equivolume of saline i.p. or drinking water only (controls) for 7, 14, 21, 28 and 42 days. As described before in our fistulas studies, assessed were the pressure required for leakage of fluid through fistula (mLH2O), diameter of the fistula defects (mm) (bladder, vaginal side).ResultsIn general, unlike poor healing in controls, BPC 157 reduced fistulas diameters (7th day) leading to the complete closure. Finally, the fistula was successfully healed in all rats underwent BPC 157 therapy (i.e., day 46, 0+/−0mm (diameter, bladder/vagina), considerable volume needed to leakage of fluid through fistula (V: 5.3+/−0.3 mL), in rats treated intraperitoneally), unlike open defects in controls: 3.1+/−0.6 (mm, bladder), 3.3+/−0.8 (mm, vagina)) diameter and small volumen sustained before leakage (V: 1.2+/−0.4 mL).ConclusionEffectiveness of BPC 157 in therapy of fistulas in rats, internal fistulas in particular, and especially in vesicovaginal fistulas, may be a particular indication for further clinical studies.Support or Funding InformationUniversity of Zagreb, Croatia (Grant number BM099)