Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pharmacol Ther. Nov 8, 2020; 11(5): 93-109
Published online Nov 8, 2020. doi: 10.4292/wjgpt.v11.i5.93
Bowel adhesion and therapy with the stable gastric pentadecapeptide BPC 157, L-NAME and L-arginine in rats
Lidija Berkopic Cesar, Slaven Gojkovic, Ivan Krezic, Dominik Malekinusic, Helena Zizek, Lovorka Batelja Vuletic, Andreja Petrovic, Katarina Horvat Pavlov, Domagoj Drmic, Antonio Kokot, Josipa Vlainic, Sven Seiwerth, Predrag Sikiric
Lidija Berkopic Cesar, Slaven Gojkovic, Ivan Krezic, Dominik Malekinusic, Helena Zizek, Antonio Kokot, Predrag Sikiric, Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb 10 000, Croatia
Lovorka Batelja Vuletic, Andreja Petrovic, Katarina Horvat Pavlov, Sven Seiwerth, Department of Pathology, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
Josipa Vlainic, Institute Ruder Boskovic, Zagreb 10000, Croatia
Author contributions: Berkopic Cesar L was involved in conceptualization and methodology; Gojkovic S took part in the visualization and investigation; Krezic I took part in the visualization and investigation; Malekinusic D provided study resources; Zizek H was involved in visualization and investigation; Batelja Vuletic L took part in the formal analysis; Petrovic A was involved in formal analysis; Horvat Pavlov K took part in the formal analysis; Drmic D provided study resources; Kokot A took part in the validation; Vlainic J was involved in conceptualization and methodology; Seiwerth S provided writing, review and editing of the manuscript; Sikiric P provided writing, review and editing of the manuscript.
Institutional animal care and use committee statement: This research was approved by local Ethic Committee (case number 380-59-10106-17-100/290) and by Directorate of Veterinary (UP/I-322-01/15-01/22).
Conflict-of-interest statement: The authors state that they have no conflicts of interest.
Data sharing statement: The data that support the findings of this study are available on request from the corresponding author.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Predrag Sikiric, MD, PhD, Professor, Department of Pharmacology, School of Medicine, University of Zagreb, Salata 11, Zagreb 10000, Croatia. sikiric@mef.hr
Received: February 13, 2020
Peer-review started: February 13, 2020
First decision: March 26, 2020
Revised: August 13, 2020
Accepted: September 10, 2020
Article in press: September 10, 2020
Published online: November 8, 2020
Processing time: 266 Days and 12.2 Hours
Abstract
BACKGROUND

After parietal peritoneum excision with an underlying superficial layer of muscle tissue in rats, there is failed vasculature, and finally, increased adhesion formation. We hypothesized that unlike nitric oxide (NO)-agents, L-NAME and/or L-arginine, the application of the stable gastric pentadecapeptide BPC 157 with its most recent vascular effects (“vascular recruitment”) means attenuated bowel adhesion formation and NO- and malondialdehyde (MDA)-tissue values.

AIM

To focused on the bowel adhesion and the therapy with the BPC 157, its most and application of NO-agents.

METHODS

Along with defect creation, medication was (1) during surgery, once, at 1 min after defect creation as an abdominal bath (1 mL/rat), BPC 157 (10 µg/kg, 10 ng/kg, 1 mL/rat), an equivolume of saline, L-NAME (5 mg/kg), L-arginine (200 mg/kg) alone and/or combined. Alternatively, medication was (2) intraperitoneally once daily, first application at 30 min after surgery, last application 24 h before assessment at d 7 or d 14. As a postponed therapy to pre-existing adhesion (3), BPC 157 (10 µg/kg, 10 ng/kg intraperitoneally, 1 mL/rat) was given once daily since d 7.

RESULTS

The recovery effect of the BPC 157 regimens goes with the presence of abundant vascular vessels in and near the defect, which occurs rapidly. Lastly, also applied as post-treatment, BPC 157 creates attenuated adhesions, minimal or no adhesion. Contrarily, NO-agents have diverse initial and final effects: The initial weakening of blood vessel disappearance and finally, severe worsening of adhesions (L-NAME) vs the initial weakening of blood vessel disappearance and finally, attenuation of adhesions formation (L-arginine), which counteract each other response given together. Importantly, BPC 157 maintains its beneficial effect also when given with NO-agents (L-NAME + BC 157; L-arginine + BPC 157; L-NAME + L-arginine + BPC 157). Finally, with respect to the increased NO- and MDA- values-adhesion tissue formation relation, unlike diverse effect of the NO-agents, the BPC 157 application effect regularly combines decrease on the increased NO- and MDA- values and the beneficial outcome (less adhesion formation).

CONCLUSION

BPC 157 therapy can be suited for the realization of the peritoneal defect healing with minimal or no adhesion formation.

Keywords: Abdominal wall defect; Adhesions; BPC 157; Vascular recruitment; Nitric oxide-agents; Rats

Core Tip: After parietal peritoneum excision with an underlying superficial layer of muscle tissue in rats, there is failed vasculature, and finally, increased adhesion formation. Unlike nitric oxide-agents, L-NAME and/or L-arginine diverse effects, the application of the stable gastric pentadecapeptide BPC 157 with its most recent described vascular effects (“vascular recruitment”) recovers abundant vascular vessel presentation in and close to the defect, which occurs rapidly. Finally, BPC 157 attenuated bowel adhesion formation and nitric oxide- and MDA-tissue values. Thus, BPC 157 therapy can be suited for the realization of the peritoneal defect healing with minimal or no adhesion formation.