Copyright
©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
Stable gastric pentadecapeptide BPC 157 in the treatment of colitis and ischemia and reperfusion in rats: New insights
Antonija Duzel, Josipa Vlainic, Marko Antunovic, Dominik Malekinusic, Borna Vrdoljak, Mariam Samara, Slaven Gojkovic, Ivan Krezic, Tinka Vidovic, Zdenko Bilic, Mario Knezevic, Marko Sever, Nermin Lojo, Antonio Kokot, Marijan Kolovrat, Domagoj Drmic, Jaksa Vukojevic, Tamara Kralj, Katarina Kasnik, Marko Siroglavic, Sven Seiwerth, Predrag Sikiric
Antonija Duzel, Josipa Vlainic, Marko Antunovic, Dominik Malekinusic, Borna Vrdoljak, Mariam Samara, Slaven Gojkovic, Ivan Krezic, Tinka Vidovic, Zdenko Bilic, Mario Knezevic, Marko Sever, Nermin Lojo, Antonio Kokot, Marijan Kolovrat, Domagoj Drmic, Jaksa Vukojevic, Tamara Kralj, Katarina Kasnik, Marko Siroglavic, Sven Seiwerth, Predrag Sikiric, Departments of Pharmacology and Pathology, Medical Faculty University of Zagreb, Zagreb 10000, Croatia
Antonija Duzel, Josipa Vlainic, Marko Antunovic, Dominik Malekinusic, Borna Vrdoljak, Mariam Samara, Slaven Gojkovic, Ivan Krezic, Tinka Vidovic, Zdenko Bilic, Mario Knezevic, Marko Sever, Nermin Lojo, Antonio Kokot, Marijan Kolovrat, Domagoj Drmic, Jaksa Vukojevic, Tamara Kralj, Katarina Kasnik, Marko Siroglavic, Sven Seiwerth, Predrag Sikiric, Medical Faculty J.J. Strossmayer University of Osijek, Osijek, Croatia; Rudjer Boskovic Institute, Department of Molecular Medicine, Zagreb 10000, Croatia
Author contributions: Duzel A, Vlainic J, Drmic D, Seiwerth S and Sikiric P designed the research; Duzel A, Vlainic J, Antunovic M, Malekinusic D, Vrdoljak B, Samara M, Gojkovic S, Krezic I, Vidovic T, Sever M, Kolovrat M, Drmic D, Vukojevic J, Kralj T, Kasnik K, Siroglavic M and Seiwerth S performed the research; Vlainic J, Seiwerth S and Sikiric P contributed reagents and analytic tools; Duzel A, Vlainic J, Vidovic T, Bilic Z, Knezevic M, Sever M, Lojo N, Kokot A, Kolovrat M, Drmic D, Vukojevic J, Seiwerth S and Sikiric P analyzed the data; Duzel A, Vlainic J, Drmic D, Seiwerth S and Sikiric P wrote the paper.
Institutional review board statement: The study was reviewed and approved by the Department of Veterinary, Ministry of Agriculture, Republic of Croatia, No: UP/I 322-01/07-01/210
Conflict-of-interest statement: The authors state that they have no conflicts of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
Correspondence to: Predrag Sikiric, MD, PhD, Professor, Department of Pharmacology, School of Medicine, University of Zagreb, Salata 11, POB 916, Zagreb 10000, Croatia.
sikiric@mef.hr
Telephone: +385-1-4566833 Fax: +385-1-4920050
Received: June 2, 2017
Peer-review started: June 6, 2017
First decision: June 22, 2017
Revised: October 31, 2017
Accepted: November 28, 2017
Article in press: November 28, 2017
Published online: December 28, 2017
Processing time: 207 Days and 18.8 Hours
AIM
To provide new insights in treatment of colitis and ischemia and reperfusion in rats using stable gastric pentadecapeptide BPC 157.
METHODS
Medication [BPC 157, L-NAME, L-arginine (alone/combined), saline] was bath at the blood deprived colon segment. During reperfusion, medication was BPC 157 or saline. We recorded (USB microscope camera) vessel presentation through next 15 min of ischemic colitis (IC-rats) or reperfusion (removed ligations) (IC + RL-rats); oxidative stress as MDA (increased (IC- and IC + RL-rats)) and NO levels (decreased (IC-rats); increased (IC + RL-rats)) in colon tissue. IC + OB-rats [IC-rats had additional colon obstruction (OB)] for 3 d (IC + OB-rats), then received BPC 157 bath.
RESULTS
Commonly, in colon segment (25 mm, 2 ligations on left colic artery and vein, 3 arcade vessels within ligated segment), in IC-, IC + RL-, IC + OB-rats, BPC 157 (10 μg/kg) bath (1 mL/rat) increased vessel presentation, inside/outside arcade interconnections quickly reappeared, mucosal folds were preserved and the pale areas were small and markedly reduced. BPC 157 counteracted worsening effects induced by L-NAME (5 mg) and L-arginine (100 mg). MDA- and NO-levels were normal in BPC 157 treated IC-rats and IC + RL-rats. In addition, on day 10, BPC 157-treated IC + OB-rats presented almost completely spared mucosa with very small pale areas and no gross mucosal defects; the treated colon segment was of normal diameter, and only small adhesions were present.
CONCLUSION
BPC 157 is a fundamental treatment that quickly restores blood supply to the ischemically injured area and rapidly activates collaterals. This effect involves the NO system.
Core tip: We rescued rat ischemic colitis. The gastric pentadecapeptide BPC 157, which has been used in clinical trials for ulcerative colitis, exerted rapid cytoprotective endothelium rescue against the disabled left colic artery and vein after blood deprivation via two ligations and during reperfusion (ligations removed). By bypassing obstructions, quickly rescuing blood supply, rapidly activating collaterals, and restoring arcade interconnections, as a new integrative beneficial effect, BPC 157 prevented the occurrence of pale lesions without mucosal folds and normalized the levels of NO and MDA, two oxidative stress markers, in tissues. BPC 157 showed effectiveness over the NO-system background, immobilized (L-NAME + L-arginine), (over)stimulated (L-arginine) or blocked (L-NAME). Likewise, later application of BPC 157 in a bath treatment to rats with pertinently obstructed vessels that underwent additional colon obstruction for three days produced a similar beneficial effect.
