Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 28, 2018; 24(48): 5462-5476
Published online Dec 28, 2018. doi: 10.3748/wjg.v24.i48.5462
Counteraction of perforated cecum lesions in rats: Effects of pentadecapeptide BPC 157, L-NAME and L-arginine
Domagoj Drmic, Mariam Samara, Tinka Vidovic, Dominik Malekinusic, Marko Antunovic, Borna Vrdoljak, Jelena Ruzman, Marija Milkovic Perisa, Katarina Horvat Pavlov, Jerusha Jeyakumar, Sven Seiwerth, Predrag Sikiric
Domagoj Drmic, Mariam Samara, Tinka Vidovic, Dominik Malekinusic, Marko Antunovic, Borna Vrdoljak, Jelena Ruzman, Marija Milkovic Perisa, Katarina Horvat Pavlov, Jerusha Jeyakumar, Sven Seiwerth, Predrag Sikiric, Departments of Pharmacology and Pathology, Medical Faculty University of Zagreb, Zagreb 10000, Croatia
Author contributions: Drmic D, Seiwerth S and Sikiric P designed the research. Drmic D, Samara M, Vidovic T, Malekinusic D, Antunovic M, Vrdoljak B, Ruzman J, Milkovic Perisa M, Horvat Pavlov K, Jeyakumar J, Seiwerth S and Sikiric P performed the research. Seiwerth S and Sikiric P contributed reagents and analytic tools. Drmic D, Samara M, Vidovic T, Malekinusic D, Antunovic M, Vrdoljak B, Ruzman J, Milkovic Perisa M, Horvat Pavlov K, Jeyakumar J, Seiwerth S and Sikiric P analyzed the data. 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/
Corresponding author: 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: August 20, 2018
Peer-review started: August 20, 2018
First decision: October 8, 2018
Revised: December 5, 2018
Accepted: December 19, 2018
Article in press: December 19, 2018
Published online: December 28, 2018
Abstract
AIM

To study the counteraction of perforated cecum lesion using BPC 157 and nitric oxide (NO) system agents.

METHODS

Alongside with the agents’ application (after 1 min, medication (/kg, 10 mL/2 min bath/rat) includes: BPC 157 (10 μg), L-NAME (5 mg), L-arginine (100mg) alone or combined, and saline baths (controls)) on the rat perforate cecum injury, we continuously assessed the gross reappearance of the vessels (USB microcamera) quickly propagating toward the defect at the cecum surface, defect contraction, bleeding attenuation, MDA- and NO-levels in cecum tissue at 15 min, and severity of cecum lesions and adhesions at 1 and 7 d.

RESULTS

Post-injury, during/after a saline bath, the number of vessels was significantly reduced, the defect was slightly narrowed, bleeding was significant and MDA-levels increased and NO-levels decreased. BPC 157 bath: the vessel presentation was markedly increased, the defect was noticeably narrowed, the bleeding time was shortened and MDA- and NO-levels remained normal. L-NAME: reduced vessel presentation but not more than the control, did not change defect and shortened bleeding. L-arginine: exhibited less vessel reduction, did not change the defect and prolonged bleeding. In combination, mutual counteraction occurred (L-NAME + L-arginine) or the presentation was similar to that of BPC 157 rats (BPC 157 + L-NAME; BPC 157 + L-arginine; BPC 157 + L-NAME + L-arginine), except the defect did not change. Thereby at day 1 and 7, saline, L-NAME, L-arginine and L-NAME + L-arginine failed (defect was still open and large adhesions present).

CONCLUSION

The therapeutic effect was achieved with BPC 157 alone or in combination with L-NAME and L-arginine as it was able to consolidate the stimulating and inhibiting effects of the NO-system towards more effective healing recruiting vessels.

Keywords: BPC 157, Perforated cecum, L-arginine, L-NAME, Vessels, Rats

Core tip: In rats, the cecum was exposed, and a perforation (5-mm diameter) was made at the ventral face of the basal region of the cecum close to the largest curvature. After 1 min, a bath (1 mL/rat) containing BPC 157, L-NAME, L-arginine, saline (controls) was directly applied to the perforated cecum, alone or in combination. Previously, BPC 157 rapidly activated the collateral circulation from existing vessels in ischemic colitis or inferior caval vein occlusion (by passing through the arcade vessels or the left ovarian vein and other veins) to reestablish blood flow and exert its free radical scavenger effect in both ischemia and reperfusion.