Bypassing major venous occlusion and duodenal lesions in rats, and therapy with the stable gastric pentadecapeptide BPC 157, L-NAME and L-arginine

Abstract

AIMTo investigate whether duodenal lesions induced by major venous occlusions can be attenuated by BPC 157 regardless nitric oxide (NO) system involvement.METHODSMale Wistar rats underwent superior anterior pancreaticoduodenal vein (SAPDV)-ligation and were treated with a bath at the ligated SAPDV site (BPC 157 10 μg, 10 ng/kg per 1 mL bath/rat; L-NAME 5 mg/kg per 1 mL bath/rat; L-arginine 100 mg/kg per 1 mL bath/rat, alone and/or together; or BPC 157 10 μg/kg instilled into the rat stomach, at 1 min ligation-time). We recorded the vessel presentation (filled/appearance or emptied/disappearance) between the 5 arcade vessels arising from the SAPDV on the ventral duodenum side, the inferior anterior pancreaticoduodenal vein (IAPDV) and superior mesenteric vein (SMV) as bypassing vascular pathway to document the duodenal lesions presentation; increased NO- and oxidative stress [malondialdehyde (MDA)]-levels in duodenum.RESULTSUnlike the severe course in the SAPDV-ligated controls, after BPC 157 application, the rats exhibited strong attenuation of the mucosal lesions and serosal congestion, improved vessel presentation, increased interconnections, increased branching by more than 60% from the initial value, the IAPDV and SMV were not congested. Interestingly, after 5 min and 30 min of L-NAME and L-arginine treatment alone, decreased mucosal and serosal duodenal lesions were observed; their effect was worsened at 24 h, and no effect on the collateral vessels and branching was seen. Together, L-NAME+L-arginine antagonized each other’s response, and thus, there was an NO-related effect. With BPC 157, all SAPDV-ligated rats receiving L-NAME and/or L-arginine appeared similar to the rats treated with BPC 157 alone. Also, BPC 157 in SAPDV-ligated rats normalized levels of NO and MDA, two oxidative stress markers, in duodenal tissues.CONCLUSIONBPC 157, rapidly bypassing occlusion, rescued the original duodenal flow through IAPDV to SMV flow, an effect related to the NO system and reduction of free radical formation.

Stable Gastric Pentadecapeptide BPC 157, Robert's Stomach Cytoprotection/Adaptive Cytoprotection/Organoprotection, and Selye's Stress Coping Response: Progress, Achievements, and the Future

“…[1][2][3][4][5][6][7][8][9][10][11][12][13] BPC 157 also acts as a free radical scavenger, counteracts free radical-induced lesions, and normalizes NO and MDA levels in tissues and during ischemia and reperfusion. 101,113,114,[116][117][118] Subsequent studies from other groups 2,96-101 have confirmed our original findings. [65][66][67][68][69][70][71][72][73][74][75][76][77][78] Pleotropic effects involving distinctive receptors, including VEGFR2 and growth hormone receptors, distinctive pathways, including VEGFR2-AKT-eNOS, ERK ½, FAK-paxillin, FoxO3a, p-AKT, p-mTOR and p-GSK-3β, and distinctive loops, including stimulation of the egr-1 gene and its corepressor gene naB2, and counteraction of increases in pro-inflammatory and procachectic cytokines, 2,[96][97][98][99][100][101] likely minimize the inherent lack of full understanding of the mechanisms that may be involved.…”

“…113 Similar evidence follows the ligation of the superior anterior pancreaticoduodenal vein and duodenal congestion lesions, which were completely counteracted by BPC 157 application, both with intraabdominal bath or intragastric application with rapid presentation of the bypassing pathway through inferior anterior pancreaticoduodenal vein to superior mesenteric vein. 117 This corresponds to the general evidence that BPC 157 was used in ulcerative colitis trial and duodenal lesions counteraction. [1][2][3][4][5][6][7][8][9][10][11][12][13] As a proof of the integrative healing evidence (rapid cytoprotective endothelium rescue that BPC 157 exerted may be useful against damaging chain of events during ischemia [two ligations] and during reperfusion [ligations removed]) appear normalized NO-and malondialdehyde (MDA)-values in colon tissues, oxidative stress markers.…”

“…But more important is the practical indicative evidence that even with the majority of studies on BPC 157 done on rodents given injection of the supplement, there are considerable number of the studies, particularly in gastrointestinal research, intragastric application or per-oral application in drinking water, correspondingly effective. 12,41,43,48,51,54,55,58,59,[61][62][63][82][83][84][85]89,[91][92][93]98,114,116,117,[143][144][145][146][147][149][150][151][152][153][154][155] In reality, in particular along with its safe profile, LD-1 not achieved, and no adverse effects in clinical trials, [1][2][3][4][5][6][7][8][9][10][11]…”

“…[1][2][3][4][5][6][7][8][9][10][11][12][13] Together, these may result in the particular activation of blood vessels during injury, vessel occlusion, or organ perforation, the recruitment of the vessel to organize an adequate shunting and bypass occlusion (indicated as=3). 101,113,117,118 Furthermore, the effect of BPC 157 is due to its interaction with and modulation of the NO system, and its interaction with prostaglandin, dopamine, and serotonin systems has also been documented. [1][2][3][4][5][6][7][8][9][10][11][12][13] BPC 157 also acts as a free radical scavenger, counteracts free radical-induced lesions, and normalizes NO and MDA levels in tissues and during ischemia and reperfusion.…”

“…The final argumentation goes to the findings that BPC 157 may have a particular additional effect during the injury on the blood vessel activity, much like vessel recruitment to circumvent the vessel occlusion, presenting an additional shunting and rapid bypassing loops to rapidly reestablish blood flow integrity. 101,113,117,118 The particular illustration to damage counteraction appears with the ischemic/reperfusion colitis, 113 and rapid bypassing loop through arcade vessels. 113 Consequently, circumventing blockades, blood flow was restored, and pale areas without mucosal folds did not occur.…”