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World J Gastroenterol. Jan 7, 2022; 28(1): 23-46
Published online Jan 7, 2022. doi: 10.3748/wjg.v28.i1.23
Cytoprotective gastric pentadecapeptide BPC 157 resolves major vessel occlusion disturbances, ischemia-reperfusion injury following Pringle maneuver, and Budd-Chiari syndrome
Predrag Sikiric, Anita Skrtic, Slaven Gojkovic, Ivan Krezic, Helena Zizek, Eva Lovric, Suncana Sikiric, Mario Knezevic, Sanja Strbe, Marija Milavic, Antonio Kokot, Alenka Boban Blagaic, Sven Seiwerth
Predrag Sikiric, Slaven Gojkovic, Ivan Krezic, Helena Zizek, Mario Knezevic, Sanja Strbe, Alenka Boban Blagaic, Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
Anita Skrtic, Eva Lovric, Suncana Sikiric, Marija Milavic, Sven Seiwerth, Department of Pathology, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
Antonio Kokot, Department of Anatomy and Neuroscience, Faculty of Medicine Osijek, J.J.Strossmayer University of Osijek, Osijek 31000, Croatia
Author contributions: Knezevic M, Kokot A, and Skrtic A designed the research study; Zizek H, Gojkovic S, and Krezic I performed the research; Milavic M, Sikiric S, and Lovric E analyzed the data; Strbe S contributed new reagents and analytic tools; Sikiric P, Seiwerth S, and Boban AB wrote the manuscript; all authors have read and approved the final manuscript.
Supported by University of Zagreb, Zagreb, Croatia, No. BM 099.
Conflict-of-interest statement: The authors state that they have no conflicts of interest to disclose.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Predrag Sikiric, MD, PhD, Full Professor, Department of Pharmacology, School of Medicine, University of Zagreb, Salata 11, Zagreb 10000, Croatia. sikiric@mef.hr
Received: March 21, 2021
Peer-review started: March 21, 2021
First decision: April 29, 2021
Revised: May 14, 2021
Accepted: December 21, 2021
Article in press: December 21, 2021
Published online: January 7, 2022
Processing time: 285 Days and 1.2 Hours
Core Tip

Core Tip: Summarizing the essential epithelium and endothelium protection interplay described in Robert’s and Szabo’s cytoprotection concept, and the role of the stable pentadecapeptide BPC 157 as a likely mediator, we suggest that BPC 157 may be a useful cytoprotective therapy. The hope is that it could finally bring into practice the huge theoretical importance of all aspects of the cytoprotection concept. Conceptually, there is a new point to discuss, namely, endothelium maintenance to epithelium maintenance (recruitment of collateral blood vessels to compensate for vessel occlusion and reestablish blood flow or bypass the occluded or ruptured vessel). BPC 157 counteracts various venous occlusion-induced syndromes, as well as inferior caval vein syndrome, ischemia-reperfusion injury following Pringle maneuver, and Budd-Chiari syndrome in rats. Activation of the alternative collateral pathways to bypass occlusion and reestablish alternative blood flow, results in the counteraction of the consequent syndromes. The severe venous occlusion-induced disturbances, the high portal and caval hypertension, aortal hypotension, arterial and venous thrombosis, both peripherally and centrally, and various organ lesions (i.e., gastrointestinal, liver, kidney, heart, and brain) were all attenuated and/or eliminated. Furthermore, this particular beneficial effect may be competing with the Virchow's triad that can be a common presentation [i.e., duodenal venous congestion lesions, perforated cecum, ischemic/reperfusion colitis, bile duct ligation-induced liver cirrhosis and portal hypertension, temporary portal triad occlusion (ischemia-reperfusion injury following the Pringle maneuver), and suprahepatic occlusion of the inferior caval vein (Budd-Chiari syndrome)]. The resolution of these various venous occlusion-induced syndromes emphasizes the evidence that as the native cytoprotective gastric peptide and a stable gastric pentadecapeptide membrane stabilizer, BPC 157, which is stable in the human gastric juice and counteracts gut-leaky syndrome, is a particular target and easily distinguished from standard peptide growth factors, involving particular molecular pathways, and specifically controlling the VEGF and NO pathways, in particular the prostaglandin pathway.