Stable Gastric Pentadecapeptide BPC 157 as a Therapy for the Disable Myotendinous Junctions in Rats.

Mladen Japjec,Andreja Prtoric,Matko Buljan,Sikiric Predrag,Miroslav Japjec,Ana Giljanovic,Eva Lovric,Andreja Petrovic,Mario Staresinic,Bozidar Sebecic,Ivan Dobric,Katarina Horvat Pavlov,Hrvoje Vranes,Anita Skrtic,Sven Seiwerth,Alenka Boban Blagaic,Domagoj Drmic,Lovorka Batelja Vuletic

doi:10.3390/biomedicines9111547

Abstract

(1) Aim: The stable gastric pentadecapeptide BPC 157 is known to heal transected muscle, tendon, and ligament. Thereby, in this study, we investigated the effect of BPC 157 on the dissection of the quadriceps tendon from the quadriceps muscle in rats. (2) Materials and Methods: Myotendinous junction defect, which cannot heal spontaneously in rats, as evidenced with consistent macro/microscopic, biomechanical, functional assessments, eNOS, and COX-2 mRNA levels and oxidative stress and NO-levels in the myotendinous junctions. BPC 157 (10 µg/kg, 10 ng/kg) regimen was given (i) intraperitoneally, first application immediately after surgery, last 24 h before sacrifice; (ii) per-orally, in drinking water (0.16 µg/mL, 0.16 ng/mL, 12 mL/rat/day), till the sacrifice at 7, 14, 28 and 42 postoperative days. (3) Results: These BPC 157 regimens document prominent therapy effects (macro/microscopic, biomechanical, functional much like eNOS and COX-2 mRNA levels and counteracted oxidative stress and NO-levels in the myotendinous junctions), while controls have a poor presentation. Especially, in rats with the disabled myotendinous junction, along with full functional recovery, BPC 157 counteracts muscle atrophy that is regularly progressive and brings muscle presentation close to normal. Accordingly, unlike the perilous course in controls, those rats, when receiving BPC 157 therapy, exhibit a smaller defect, and finally defects completely disappear. Microscopically, there are no more inflammatory infiltrate, well-oriented recovered tissue of musculotendon junction appears in BPC 157 treated rats at the 28 days and 42 days. (4) Conclusions: BPC 157 restores myotendinous junction in accordance with the healing of the transected muscle, tendon, and ligament.

Highlights

We evidenced that the stable gastric pentadecapeptide BPC 157 recovers myotendinous junction, likely with the functional recovery, muscle size recovery, and counteraction of the oxidative stress, and particular effect on COX 2, nNOS, iNOS, eNOS mRNA levels in the dissected myotendinous junction (Figures 1–15)
The injured rats remain largely disabled after careful dissecting of the quadriceps tendon from the quadriceps muscle, unable to compensate for failed crucial knee extensor
The injured rats definitely remain largely disabled after careful dissecting of quadriceps tendon from the quadriceps muscle, unable to compensate failed crucial knee extensor

Summary

Introduction

In tendon and muscle healing, the lack of therapy studies upon myotendinous junction injury may be due to the apparent inconsistencies between the suggested various growth factors high physiologic significance [23] and not achieved practical realization of the supposed healing effect [23]. Unlike BPC 157 native peptide therapy [3,4,5,6,7,8,9,10,11,12,13,14,15,16,17], there is a lacking easy practical applicability for many various growth factors that have been suggested to be necessary for natural healing [23]. The illustrative attempts include both highly sophisticated delivery technics (i.e., a suture carrying nanoparticle/pEGFP-basic fibroblast growth factor (bFGF) and pEGFP-vascular endothelial growth factor A (VEGFA)

Methods

Results

Conclusion