Therapy Effect of the Stable Gastric Pentadecapeptide BPC 157 on Acute Pancreatitis as Vascular Failure-Induced Severe Peripheral and Central Syndrome in Rats

Abstract

We revealed the therapy effect of the stable gastric pentadecapeptide BPC 157 (10 μg/kg, 10 ng/kg ig or po) with specific activation of the collateral rescuing pathways, the azygos vein, on bile duct ligation in particular, and acute pancreatitis as local disturbances (i.e., improved gross and microscopy presentation, decreased amylase level). Additionally, we revealed the therapy’s effect on the acute pancreatitis as vascular failure and multiorgan failure, both peripherally and centrally following “occlusion-like” syndrome, major intoxication (alcohol, lithium), maintained severe intra-abdominal hypertension, and myocardial infarction, or occlusion syndrome, and major vessel occlusion. The application-sacrifice periods were ligation times of 0–30 min, 0–5 h, 0–24 h (cured periods, early regimen) and 4.30 h–5 h, 5 h–24 h (cured periods, delayed regimen). Otherwise, bile duct-ligated rats commonly presented intracranial (superior sagittal sinus), portal and caval hypertension and aortal hypotension, gross brain swelling, hemorrhage and lesions, heart dysfunction, lung lesions, liver and kidney failure, gastrointestinal lesions, and severe arterial and venous thrombosis, peripherally and centrally. Unless antagonized with the key effect of BPC 157 regimens, reversal of the inferior caval and superior mesenteric vein congestion and reversal of the failed azygos vein activated azygos vein-recruited direct delivery to rescue the inferior-superior caval vein pathway; these were all antecedent to acute pancreatitis major lesions (i.e., acinar, fat necrosis, hemorrhage). These lesions appeared in the later period, but were markedly attenuated/eliminated (i.e., hemorrhage) in BPC 157-treated rats. To summarize, while the innate vicious cycle may be peripheral (bile duct ligation), or central (rapidly developed brain disturbances), or peripheral and central, BPC 157 resolved acute pancreatitis and its adjacent syndrome.

Stable Gastric Pentadecapeptide BPC 157 as Useful Cytoprotective Peptide Therapy in the Heart Disturbances, Myocardial Infarction, Heart Failure, Pulmonary Hypertension, Arrhythmias, and Thrombosis Presentation

“…Unlike the effectiveness only given before injury (prophylactic effect) of the standard cytoprotective agents (for review, see, i.e., [10,11]), BPC 157, in addition to its prophylactic effect, has a strong curative effect given even much later after injury induction, during ischemia as well as during reperfusion (for review, see, i.e., [2][3][4][5][6][7][8]). Illustratively, as mentioned before, in the vascular studies, as a part of the severe vascular and multiorgan failure syndrome counteraction, there was counteraction of the brain, heart, lung, liver, kidney, and gastrointestinal lesions [18,19,23,24,[27][28][29]31,[37][38][39][40]. Moreover, in other separate studies, there was counteraction of the brain [83], spinal cord [35,36], heart failure [84], lung [41,[85][86][87], liver lesions [88][89][90], liver, gastrointestinal and brain lesions [91][92][93][94][95][96], and kidney [97][98][99] and pancreas [100,101] lesions.…”

“…Thus, these disturbances, and consequently, the beneficial counteraction by BPC 157 therapy, may have a general significance [38]. Commonly, these disturbances [38], presented as shared occlusion-like and occlusion syndromes [19,24,27,29,31,[37][38][39][40], may provide additional prototypes for the heart lesions, vascular failure, and therapy possibilities. Of note, all of these disturbances were consistently attenuated with BPC 157 therapy application and the activation of the collateral pathways, relayed on the given injury .…”

“…Table 1. Summarized presentation of the BPC 157 therapy effect on myocardial infarction and heart failure that were induced in the vascular studies [19,24,27,29,31,[37][38][39][40][41]. Permanently occluded essential vessel tributaries, both arterial and venous, occluded superior mesenteric vein and artery in rats Escalated general peripheral and central syndrome Severe myocardial congestion, along with subendocardial infarcts [29] BPC 157 rapidly activated collateral pathways.…”

“…It should be noted that to verify the suggested peripheral and central interplay, the studies also implied several routes of BPC 157 application, with equipotent beneficial therapy effect [19,[22][23][24][27][28][29]31,[37][38][39][40]. Local application at the swollen brain implies a direct effect; intraperitoneal or intragastric administrations mean a systemic effect; µgand ng-regimens mean a common beneficial effect [27].…”

“…Thus, in general terms, given its easy applicability (including via a therapeutic per-oral regimen), BPC 157 therapy leads to the upgraded minor vessel taking over the function of the failed major vessel to compensate and reestablish the reorganized blood flow , which occurs as the recovery of endothelium function [2][3][4][5][6][7][8]. Thereby, with BPC 157 "bypassing key", there were reported the prevention and the reversal of the myocardial infarction (for review, see, i.e., [19,24,27,29,31,[37][38][39][40]), arrhythmias (for review, see, i.e., [19,[22][23][24][27][28][29]31,[37][38][39][40][41]), and from different origins, heart failure [19,24,27,29,31,[37][38][39][40][41] and pulmonary hypertension [41] and thrombosis [18,19,23,24,[27][28][29]31,[37]…”