Cytoprotective gastric pentadecapeptide BPC 157 resolves major vessel occlusion disturbances, ischemia-reperfusion injury following Pringle maneuver, and Budd-Chiari syndrome

Abstract

The stable gastric pentadecapeptide BPC 157 counteracts various venous occlusion-induced syndromes. Summarized are all these arguments, in the Robert’s cytoprotection concept, to substantiate the resolution of different major vessel occlusion disturbances, in particular ischemia-reperfusion injury following the Pringle maneuver and Budd-Chiari syndrome, which was obtained by BPC 157 therapy. Conceptually, there is a new point, namely, endothelium maintenance to epithelium maintenance (the recruitment of collateral blood vessels to compensate for vessel occlusion and reestablish blood flow or bypass the occluded or ruptured vessel). In this paper, we summarize the evidence of the native cytoprotective gastric pentadecapeptide BPC 157, which is stable in the human gastric juice, is a membrane stabilizer and counteracts gut-leaky syndrome. As a particular target, it is distinctive from the standard peptide growth factors, involving particular molecular pathways and controlling VEGF and NO pathways. In the early 1990s, BPC 157 appeared as a late outbreak of the Robert’s and Szabo’s cytoprotection-organoprotection concept, like the previous theoretical/practical breakthrough in the 1980s and the brain-gut axis and gut-brain axis. As the time went on, with its reported effects, it is likely most useful theory practical implementation and justification. Meantime, several reviews suggest that BPC 157, which does not have a lethal dose, has profound cytoprotective activity, used to be demonstrated in ulcerative colitis and multiple sclerosis trials. Likely, it may bring the theory to practical application, starting with the initial argument, no degradation in human gastric juice for more than 24 h, and thereby, the therapeutic effectiveness (including via a therapeutic per-oral regimen) and pleiotropic beneficial effects.

Keywords: Gastric pentadecapeptide BPC 157; Cytoprotection; Major vessel occlusion disturbances; Pringle maneuver; Budd-Chiari syndrome; Therapy

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.