Counteraction of perforated cecum lesions in rats: effects of pentadecapeptide BPC 157, L-NAME and L-arginine

Abstract

AIMTo study the counteraction of perforated cecum lesion using BPC 157 and nitric oxide (NO) system agents.METHODSAlongside 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.RESULTSPost-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).CONCLUSIONThe 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.

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.…”

“…1). While introducing a new concept BPC 157 first strictly follows, and then, it considerably extends, with recently demonstrated recruitment of blood vessels to bypass vascular occlusion, 101,113,117,118 the guidelines of classic of stomach cells/endothelium cytoprotection [14][15][16][17][18][19][20][21] and Selye's concept of stress response against stress injury to reestablish disturbed homeostasis. [22][23][24][25]40 Thus, in practice, these findings may be relevant to resolving Robert's cytoprotection/adaptive cytoprotection/organoprotection, [14][15][16][17][18][19][20][21] and consequently, Selye's stress coping response, [22][23][24][25]40 and practical applicability.…”

“…[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.…”

“…101 Interestingly, after cecum perforation, with BPC 157 administration we documented the gross reappearance of the vessels (USB micro camera) quickly propagating toward the defect at the caecum surface, defect in contraction, bleeding attenuation, MDA-and NO-levels normalized in colon tissue at 15 minutes, and advanced healing of colon lesions and less adhesions at days 1 and 7. 118 Robert's stomach cytoprotection concept as the peripheral part of the brain-gut axis as beneficial background for the BPC 157 application in various CNS-disorders…”