The effects of pentadecapeptide BPC 157 in stress urinary incontinence models in female rats

Abstract

Pozadina: Na osnovi prethodno ustanovljenih promotivnih učinaka stabilnog želučanog pentadekapeptida BPC 157 (PL 14736) na tkivno specifične procese cijeljenja, npr. skeletnih poprečno-prugastih te glatkih mišića gastrointestinalnog trakta, napose sfinktera, kao i živčanog tkiva, u ovom je radu istraživan njegov učinak na oporavak urodinamskog parametra LPP (eng. leak point pressure) u štakorskim modelima stresne urinarne inkontinencije (SUI) s transabdominalnom uretrolizom (TU) i protrahiranom vaginalnom dilatacijom (VD), uz praćenje histoloških promjena na uretrama eksperimentalnih životinja. ----- Materijali/Metode: Tretman s pentadekapeptidom BPC157 provođen je u trajanju od 7 dana i kod zdravih i kod operiranih životinja (TU ili VD), i to (i) intraperitonealno, 10 µg/kg ili 10 ng/kg, (prva doza 30 minuta nakon operacije, posljednja 24 sata prije mjerenja LPP-a i žrtvovanja), ili (ii) peroralno, 10 µg/kg otopljen u vodi za piće (0.16 µg/mL, 12 mL po štakoru po danu). Kontrolne životinje primale su ekvivolumno (5 mL/kg) intraperitonealno čistu fiziološku otopinu, odnosno, peroralno, standardnu vodu za piće. Vezikouretralni segmenti preuzeti su za imunohistokemijsku analizu. ----- Rezultati: Svi režimi terapije s BPC 157 spriječile su pad u vrijednostima LPP-a nakon TU i VD. Dodatno, pojedine skupine s mikrogramskim dozama (peroralno i intraperitonealno kod TU, te intraperitonealno kod VD) dosižu vrijednosti LPP-uočene kod zdravih životinja. U zdravih životinja, terapija s BPC 157 nije alterirala vrijednosti LPP-a. Imunohistokemijske analize uretri životinja tretiranih s BPC 157 pokazale su, u odnosu na kontrole, veću pozitivnost za dezmin (prikaz udjela poprečno-prugastih mišićnih vlakana), glatkomišićni aktin te za CD34 (marker angiogeneze), kao i sačuvan omjer ukupnog mišićnog i vezivnog tkiva (bojanje Mallory trikrom metodom). ----- Zaključci: Pentadekapeptid BPC 157 primijenjen peoralno ili intra-peritonealno ima terpijske učinke na SUI, funkcionalno i histološki korigirajući inače dertimentalan tijek nakon TU i VD. Demonstrirani učinci mogu predstavljati osnov za buduće strategije terapijsko-prevencijskog pristupa SUI.Background: Since an originally anti-ulcer stable gastric penta-decapeptide BPC 157 (PL 14736) was shown to promote healing of injured striated muscle and also smooth muscle in the gastrointestinal tract, we explored its therapeutic potentials for leak point pressure (LPP) recovery in rat stress urinary incontinence (SUI) after transabdominal urethrolysis (TU) and prolonged vaginal dilatation (VD), along with urethral histology assessment. ----- Materials/Methods: During a 7-day period, TU-rats and VD-rats (or healthy rats) received BPC 157, either (i) intraperitoneally, 10 µg/kg or 10 ng/kg, once daily (first administration 30 min after surgery, last 24 h before LPP-testing and sacrifice), or (ii) per-orally, 10 µg/kg in drinking water (0.16 µg/mL, 12 mL/rat/day). Controls received only drinking water or an equal volume of saline (5 mL/kg, intraperitoneally). Vesicourethral segments were harvested for immunohistochemical evaluation. ---- Results: All BPC 157 regimens counteracted decrease of LPP values in TU-rats and VD-rats. Additionally, BPC 157-TU rats (µg-intraperitoneally or per-orally) and BPC 157-VD rats (µg intraperitoneally) reached LPP values originally noted in healthy rats. Conversely, in healthy rats, BPC 157 did not alter LPP. Immunohistochemical studies revealed higher desmin (delineates striated organization of skeletal muscle), smooth muscle actin, and CD34 (angiogenic marker) positivity within the urethral wall in BPC 157-treated rats vs. controls, as well as overall preserved muscle/connective tissue ratio assessed with Mallory’s trichrome staining. ----- Conclusions: Pentadecapeptide BPC 157, applied parenterally or per-orally, appears to ameliorate the SUI in rat models, improving the otherwise detrimental course of healing after VD and TU, which may be analogous to human injury. These beneficial effects may possibly be selectively used in future strategies for treatment of SUI