Occlusion of the Superior Mesenteric Artery in Rats Reversed by Collateral Pathways Activation: Gastric Pentadecapeptide BPC 157 Therapy Counteracts Multiple Organ Dysfunction Syndrome; Intracranial, Portal, and Caval Hypertension; and Aortal Hypotension

Abstract

Gastric pentadecapeptide BPC 157 therapy counteracts multiple organ dysfunction syndrome in rats, which have permanent occlusion of the superior mesenteric artery close to the abdominal aorta. Previously, when confronted with major vessel occlusion, its effect would rapidly activate collateral vessel pathways and resolve major venous occlusion syndromes (Pringle maneuver ischemia, reperfusion, Budd–Chiari syndrome) in rats. This would overwhelm superior mesenteric artery permanent occlusion, and result in local, peripheral, and central disturbances. Methods: Assessments, for 30 min (gross recording, angiography, ECG, pressure, microscopy, biochemistry, and oxidative stress), included the portal hypertension, caval hypertension, and aortal hypotension, and centrally, the superior sagittal sinus hypertension; systemic arterial and venous thrombosis; ECG disturbances; MDA-tissue increase; and multiple organ lesions and disturbances, including the heart, lung, liver, kidney, and gastrointestinal tract, in particular, as well as brain (cortex (cerebral, cerebellar), hypothalamus/thalamus, hippocampus). BPC 157 therapy (/kg, abdominal bath) (10 µg, 10 ng) was given for a 1-min ligation time. Results: BPC 157 rapidly recruits collateral vessels (inferior anterior pancreaticoduodenal artery and inferior mesenteric artery) that circumvent occlusion and ascertains blood flow distant from the occlusion in the superior mesenteric artery. Portal and caval hypertension, aortal hypotension, and, centrally, superior sagittal sinus hypertension were attenuated or eliminated, and ECG disturbances markedly mitigated. BPC 157 therapy almost annihilated venous and arterial thrombosis. Multiple organ lesions and disturbances (i.e., heart, lung, liver, and gastrointestinal tract, in particular, as well as brain) were largely attenuated. Conclusions: Rats with superior mesenteric artery occlusion may additionally undergo BPC 157 therapy as full counteraction of vascular occlusion-induced multiple organ dysfunction syndrome.

Physiological and Immunological Status of Adult Honeybees (Apis mellifera) Fed Sugar Syrup Supplemented with Pentadecapeptide BPC 157

“…It exerts intestines endothelium protection and counteracts gastrointestinal lesions in rats and mice [ 19 ]. Of particular importance for the intestine integrity may be the therapy which activate collateral pathways to recovery occlusive syndromes [ 25 , 26 , 27 ]. The molecular mechanisms of BPC have been studied in numerous studies including altered genes expression, angiogenesis, NO-system, oxidative stress markers, or prostaglandins system [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ].…”

Stable Gastric Pentadecapeptide BPC 157 Heals Established Vesicovaginal Fistula and Counteracts Stone Formation in Rats

“…However, considering the proposed essential role of the ischemia in the falling course of the vesicovaginal fistulas [14], it may be stated that BPC 157 exhibits a particular effect on blood vessels [1][2][3][4], and may rapidly activate collateral pathways to circumvent major vessel occlusion, and reestablish blood flow and compensate otherwise imminent ischemic consequences. There is rapid counteracting effect noted in various severe permanent occlusion of major vessels-induced occlusive syndromes [47][48][49][50][51][52]. Likewise, BPC 157 maintained thrombocytes function (without interference with coagulation) [53][54][55], prevented thrombosis formation, and abrogated already advanced thrombosis that may be associated with vessels lesions [56] or occlusion [47][48][49][50][51][52], arterial [36,50,51], or venous [47][48][49]51,52] as well as arterial and venous [51], peripherally [47][48][49][50][51], or centrally [52].…”

“…There is rapid counteracting effect noted in various severe permanent occlusion of major vessels-induced occlusive syndromes [47][48][49][50][51][52]. Likewise, BPC 157 maintained thrombocytes function (without interference with coagulation) [53][54][55], prevented thrombosis formation, and abrogated already advanced thrombosis that may be associated with vessels lesions [56] or occlusion [47][48][49][50][51][52], arterial [36,50,51], or venous [47][48][49]51,52] as well as arterial and venous [51], peripherally [47][48][49][50][51], or centrally [52]. These vascular effects that may be especially relevant for the fistulas healing [3], were associated with the particular effect on several molecular pathways [18][19][20][21][22][23][24][25][26][27], in particular, having a modulatory effects on NO-system and prostaglandins-system [56,57] and on va...…”

“…These vascular effects that may be especially relevant for the fistulas healing [3], were associated with the particular effect on several molecular pathways [18][19][20][21][22][23][24][25][26][27], in particular, having a modulatory effects on NO-system and prostaglandins-system [56,57] and on vasomotor tone and the activation of Src-Caveolin-1-eNOS pathway [21]. Besides, BPC 157 acts as stabilizer of cellular junctions [19], and free radical scavenger [39,58,59], and counteracted free radicals formation and lesions, in particular, in vascular occlusion studies [47][48][49][50][51][60][61][62][63]. Illustratively, the BPC 157 activity as stabilizer of cellular junction (counteracted leaky gut syndrome) goes via increasing tight junction protein ZO-1 expression, and transepithelial resistance [19].…”

“…Finally, considering the presented and previous findings in fistula research [5][6][7][8][9][10], this study should overwhelm the general point that animal studies per se may be cautious, and fistulas studies; in particular, regarding their results and the relative paucity of the BPC 157 clinical data [1][2][3][4]. On the other hand, BPC 157 was proved to be efficacious in the ulcerative colitis, both in clinical settings [65,66], and in the experimental rats studies, in the ischemic/reperfusion vascular ulcerative colitis studies [60] and other ulcerative colitis models, induced by TNBS [67], cysteamine, surgery [31,68,69], NSAIDs [30,[70][71][72][73], or major vessel occlusion [48][49][50][51][52]59], including various species [74], and fistulas as complications (for review see, i.e., [3]). A particular point for revealing and applying this concept in practice (BPC 157's beneficial effect on various fistulas toward counteraction of the vesicovaginal fistulas in particular) is a very safe profile (LD1 could be not achieved) [17], a point recently confirmed in a large study of the Xu and collaborators [75].…”