BPC 157 Rescued NSAID-cytotoxicity Via Stabilizing Intestinal Permeability and Enhancing Cytoprotection

Abstract

: The stable gastric pentadecapeptideBPC 157 protects stomach cells, maintains gastric integrity against various noxious agents such as alcohol, nonsteroidal anti-inflammatory drugs (NSAIDs), and exerts cytoprotection/adaptive cytoprotection/organoprotection in other epithelia, that is, skin, liver, pancreas, heart, and brain. Especially BPC 157 counteracts gastric endothelial injury that precedes and induces damage to the gastric epithelium and generalizes "gastric endothelial protection" to protection of the endothelium of other vessels including thrombosis, prolonged bleeding, and thrombocytopenia. In this background, we put the importance of BPC 157 as possible way of securing GI safety against NSAIDsinduced gastroenteropathy since still unmet medical needs to mitigate NSAIDs-induced cytotoxicity are urgent. Furthermore, gastrointestinal irritants such as physical or mental stress, NSAIDs administration, surfactants destroyer such as bile acids, alcohol can lead to leaky gut syndromethrough increasingepithelial permeability. In this review article, we described the potential rescuing actions of BPC 157 against leaky gut syndrome after NSAIDs administration for the first time.

BPC 157 as a Therapy for Retinal Ischemia Induced by Retrobulbar Application of L-NAME in Rats

“…Activation of the VEGFR2-Akt-eNOS signaling pathway goes without the need of other known ligands or shear stress ( Hsieh et al, 2017 ). In addition, BPC 157 may act as a free radical scavenger ( Belosic Halle et al, 2017 ; Duzel et al, 2017 ; Luetic et al, 2017 ; Amic et al, 2018 ; Drmic et al, 2018 ; Vukojevic et al, 2018 ; Sever et al, 2019 ; Sucic et al, 2019 ; Kolovrat et al, 2020 ; Park et al, 2020 ). In particular, BPC 157 reestablished NO-values in the occluded inferior caval vein and ischemic colon tissue, as well as counteracted increased MDA values ( Duzel et al, 2017 ; Vukojevic et al, 2018 ).…”

“…Accordingly, there is an important common understanding that any form of treatment that can enhance the natural cellular antioxidant defense system should have a neuroprotective action in retinal ischemia ( Osborne et al, 2004 ). Finally, the role of BPC 157 as the stabilizer of cellular junction is well founded ( Park et al, 2020 ). It acts via increasing tight junction protein ZO-1 expression and transepithelial resistance.…”

“…It acts via increasing tight junction protein ZO-1 expression and transepithelial resistance. Specifically, BPC 157 inhibited the mRNA of inflammatory mediators (iNOS, IL-6, IFNγ, and TNF-α), increased the expression of HSP 70 and 90, and antioxidant proteins (such as HO-1, NQO-1, glutathione reductase, glutathione peroxidase 2, and GST-pi) ( Park et al, 2020 ). Consequently, it may effectively counteract ischemia-induced increased capillary permeability also in the rats damaged by retrobulbar L-NAME administration.…”

“…This particular point supports the recent evidence that vasomotor tone is carried out through BPC 157–specific activation of the Src-Caveolin-1-endothelial NOS (eNOS) pathway ( Hsieh et al, 1997 ). Likewise, BPC 157 has a modulatory role ( Sikiric et al, 2014 ) (in particular, to the blood pressure ( Sikiric et al, 1997 ) and thrombocytes function maintenance ( Stupnisek et al, 2012 , 2015 ; Konosic et al, 2019 )) and additional interaction with several molecular pathways ( Tkalcevic et al, 2007 ; Chang et al, 2011 , 2014 ; Hsieh et al, 2017 ; 2020; Kang et al, 2018 ; Vukojevic et al, 2018 ; Vukojevic et al, 2020 ; Park et al, 2020 ; Wu et al, 2020 ) [i.e., activation of the VEGFR2-Akt-eNOS signaling pathway without the need of other known ligands or shear stress ( Hsieh et al, 2017 )]. To illustrate its modulatory role on NO-system functions ( Sikiric et al, 2014 ), BPC 157 may counteract L-NAME hypertension and pro-thrombotic effect as well as L-arginine hypotension and antithrombotic effect ( Sikiric et al, 1997 ; Stupnisek et al, 2015 ), and induce its own NO-release ( Sikiric et al, 1997 ; Turkovic et al, 2004 ).…”

“…To illustrate its modulatory role on NO-system functions ( Sikiric et al, 2014 ), BPC 157 may counteract L-NAME hypertension and pro-thrombotic effect as well as L-arginine hypotension and antithrombotic effect ( Sikiric et al, 1997 ; Stupnisek et al, 2015 ), and induce its own NO-release ( Sikiric et al, 1997 ; Turkovic et al, 2004 ). Also, BPC 157 may be the free radical scavenger to counteract reperfusion-induced free radical injury ( Belosic Halle et al, 2017 ; Duzel et al, 2017 ; Luetic et al, 2017 ; Amic et al, 2018 ; Drmic et al, 2018 ; Vukojevic et al, 2018 ; Sever et al, 2019 ; Sucic et al, 2019 ; Kolovrat et al, 2020 ; Park et al, 2020 ). In addition, BPC 157, as an agent with cytoprotective effect in the entire gastrointestinal tract (and thereby, innate endothelium protection) ( Sikiric et al, 2018 ; Sikiric et al, 2020 ), prevents and reverses thrombosis formation ( Hrelec et al, 2009 ; Vukojevic et al, 2018 ; Gojkovic et al, 2020 ; Kolovrat et al, 2020 ).…”