Stable Gastric Pentadecapeptide BPC 157: Comparison
Please note this is a comparison between Version 2 by Dean Liu and Version 1 by Predrag Sikiric.

Stable gastric pentadecapeptide BPC 157 especial therapy effects combine the therapy of myocardial infarction, heart failure, pulmonary hypertension arrhythmias, and thrombosis prevention and reversal. The shared therapy effect occurred as part of its even larger cytoprotection (cardioprotection) therapy effect (direct epithelial cell protection; direct endothelium cell protection) that BPC 157 exerts as a novel cytoprotection mediator, which is native and stable in human gastric juice, as well as easily applicable.

  • stable gastric pentadecapeptide BPC 157
  • peptide therapy
  • hearth disturbances

1. Introduction

Numerous key clinical trials published or presented at major international conferences over the course of 2021 were reviewed as the most valuable contributions to clinical cardiology (for review, see, i.e., [1]). Heart failure data focused on trials with sodium–glucose cotransporter 2 (SGLT2) inhibitors, sacubitril/valsartan, and mavacamten for hypertrophic cardiomyopathy [1]. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were centered in the prevention trials [1].
On the other hand, as a new attempt, from the cytoprotection viewpoint and potential involvement of the cytoprotective agents, we authors reviewed the potential significance in the heart disturbances of the therapy with the stable gastric pentadecapeptide BPC 157 (for review, see, i.e., [2,3,4,5,6,7,8,9][2][3][4][5][6][7][8][9]). It appeared, as a peptide native and stable in human gastric juice, as a late outbreak of the cytoprotection/organoprotection concept of Robert and Szabo, a concept mostly from the stomach studies [10,11,12,13,14,15,16,17][10][11][12][13][14][15][16][17] for epithelial and endothelial protection, like the previous theoretical/practical breakthroughs in the 1980s and brain–gut axis and gut–brain axis (for review, see, i.e., [2,3,4,5,6,7,8][2][3][4][5][6][7][8]). However, its compelling basic highlights (particular vascular effect, activation of the collateral pathways) [18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] in the most valuable animal models might still need confirmation as the vast clinical evidence obtained in the huge number of clinical trials [1]. Nevertheless, it might challenge further therapy use.

2. Cytoprotection Background (Direct Epithelial Cell Protection) for BPC 157 Beneficial Activity

The wide applicability of the original postulates of Robert and Szabo’s cytoprotection concept (for review, see, i.e., [10,11,12,13,14,15,16,17][10][11][12][13][14][15][16][17]) might approach the entire problem of heart failure. This wide approach might be useful as a large number of the concomitant diseases with heart failure might be the key for the therapeutic effects [77[42][43][44],78,79], as the stable gastric pentadecapeptide BPC 157 pleiotropic effect belongs to the cytoprotective class of agents (for review, see, i.e., [2,3,4,5,6,7,8][2][3][4][5][6][7][8]). Note the general background of the BPC 157 beneficial effects on various organs injuries (for review, see, i.e., [2,3,4,5,6,7,8][2][3][4][5][6][7][8]), which helps one recognize the wide significance of the cytoprotection concept of Robert’s (direct epithelial cell protection) [10] and Szabo’s (direct endothelium cell protection) [12] that is initiated in the stomach to be further generalized. The foundation of the cytoprotective agents’ putative activities in the stomach studies was the initial basic point for their possible therapy extension [10,11,12,13,14,15,16,17][10][11][12][13][14][15][16][17]. In general, BPC 157 successfully follows the common cytoprotective principle: the original cytoprotective agent with a prime beneficial effect in the stomach (direct (epithelial) cell protection) had to be transmitted to similar beneficial effect in other organ lesions as well (cytoprotection → organoprotection) [10,11,12,13,14,15,16,17][10][11][12][13][14][15][16][17] (for review, see, i.e., [2,3,4,5,6,7,8][2][3][4][5][6][7][8]). Noteworthily, BPC 157 therapy, in practical terms (native and stable in human gastric juice for more than 24 h, and, thereby, easily applicable), unlike standard cytoprotective agents, fully presumes original cytoprotective requirements (for review, see, i.e., [2,3,4,5,6,7,8][2][3][4][5][6][7][8]). Thereby, the extent of the obtained beneficial effects largely overrides the range of the beneficial effects commonly reported with the standard cytoprotective agents (for review, see, i.e., [2,3,4,5,6,7,8][2][3][4][5][6][7][8]) (i.e., prostaglandins’ beneficial effects on stomach [10], intestine [13], liver [80][45], pancreas [13], kidney [81][46], and heart [82][47]). Unlike the effectiveness only given before injury (prophylactic effect) of the standard cytoprotective agents (for review, see, i.e., [10,11][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][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][18][19][23][24][27][28][29][31][37][38][39][40]. Moreover, in other separate studies, there was counteraction of the brain [83][48], spinal cord [35[35][36],36], heart failure [84][49], lung [41,85,86[41][50][51][52],87], liver lesions [88[53][54][55],89,90], liver, gastrointestinal and brain lesions [91[56][57][58][59][60][61],92,93,94,95,96], and kidney [97,98,99][62][63][64] and pancreas [100,101][65][66] lesions. There was also a strong wound-healing effect (for review, see, i.e., [3,102][3][67]). Thereby, there was the curing of the skin [53[68][69][70][71][72],55,103,104,105], nerve [106][73], tendon [50[74][75][76][77][78][79][80],51,107,108,109,110,111], muscle [110[79][80][81][82][83][84],111,112,113,114,115], ligament [116][85], and bone [117,118,119][86][87][88] injuries that spontaneously might not heal. In particular, there was a capability to simultaneously organize the healing of the different tissues (as an example occurred the healing of the osteotendinous junction [108,109][77][78] and the healing of the myotendinous junction [111][80] (and neuromuscular junction function recovering [68][89]) or the healing of the fistulas, external and internal [120][90]). Likewise, in particular regard for wounding [3[3][67],102], these realized healing effects in the various wounds [53,55,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120][68][69][70][71][72][73][76][77][78][79][80][81][82][83][84][85][86][87][88][90] might evidence the realized healing process after blood vessel are ruptured as a whole, and thereby, as we claimed [59][91], a distinctive effect on all four major events in clot formation and dissolution was fully accomplished. This meant a highly utilizable special effect, especially with heart failure therapy [18,19,23,24,27,28,29,31,37,38,39,40][18][19][23][24][27][28][29][31][37][38][39][40]. Moreover, BPC 157 is very safe, with no adverse effect in clinical trials (i.e., ulcerative colitis), and lethal dose (LD1) was not achieved in toxicology studies (for review, see, i.e., [2,3,4,5,6,7,8][2][3][4][5][6][7][8]). Thereby, these beneficial effects (for review, see, i.e., [2,3,4,5,6,7,8][2][3][4][5][6][7][8]) fulfill the cytoprotection (organoprotection) frame at the general level (implied direct cell protection) [10[10][11][12][13][14][15][16][17],11,12,13,14,15,16,17], with all of the mentioned beneficial effects as pre-requests for the resolved heart disturbances. In these terms, the effect on the heart (cardioprotection) might be an additional part of the cytoprotective activity (for review, see, i.e., [10,11,12,13,14,15,16,17,121,122,123][10][11][12][13][14][15][16][17][92][93][94]), and, in particular, it might be commonly taken as proof and consequence of its innate cytoprotective activity (for review, see, i.e., [2,3,4,5,6,7,8][2][3][4][5][6][7][8]). In addition to being native and stable in human gastric juice for more than 24 h, BPC 157 was found in situ hybridization and immunostaining studies in humans to be largely distributed in tissues [3,102][3][67] and may have additional physiologic regulatory roles [8,102][8][67] as it is thought to be a novel cytoprotective mediator. Furthermore, there is a particular healing effect depending on the tissue involved (for review, see, i.e., [3,102][3][67]). Particularly, there is an improved healing effect (for review, see, i.e., [3,102][3][67]) for eye injuries (no angiogenesis) [124][95] versus advanced angiogenesis in other tissues (i.e., tendon, muscle) [110][79] (for review, see, i.e., [3,102][3][67]), which together might provide evidence that BPC 157s beneficial effect is even more complex and tissue specific. Illustratively, BPC 157 eye drops successfully closed perforating corneal incisions in rats; controls developed new vessels that grew from the limbus to the penetrated area, whereas BPC 157-treated rats generally had no new vessels, and those that did form in the limbus did not make contact with the penetrated area [124][95]. Thus, important for heart healing as well, BPC 157 certainly might control one of the most important aspects of the cytoprotection and cytoprotective agents activity in long terms (i.e., days): the angiogenesis (corneal avascularity as “angiogenic privilege”) (for review, see, i.e., [3,102][3][67]).

3. Cytoprotection Background (Direct Endothelial Cell Protection) for BPC 157 Beneficial Activity

Overwhelmingly focused on stomach cytoprotection, the pioneers, Robert (direct epithelial cell protection) [10] and Szabo (direct endothelium cell protection) [11], estimated in stomach damage studies the maxim endothelium maintenance → epithelium maintenance as rapid injury, rapid defensive response, vascular injury within less than 1 min, thrombus and stasis [11], thereby, although not claimed, Virchow triad circumstances. Moreover, finally, the rapid recovery of damaged endothelium occurred as a shared effect of the cytoprotective agents within stomach cytoprotection [11]. With BPC 157 effect (see above), there is an advanced practical realization of the original maxim functioning [8]. This might be the rapid upgrading of the minor vessel to take over the function of the disabled major vessel [18[18][19][23][24][27][28][29][31][37][38][39][40],19,23,24,27,28,29,31,37,38,39,40], as the particular effect on the vessel relied on the given injury. Furthermore, this implies competing with the Virchow triad circumstances devastatingly present, making possible the recruitment of collateral blood vessels, compensating vessel occlusion, and reestablishing blood flow or bypassing the occluded or ruptured vessel [18,19,23,24,27,28,29,31,37,38,39,40][18][19][23][24][27][28][29][31][37][38][39][40]. Illustrative examples might be the therapy of glaucoma in rats after the cauterization of three of the four episcleral veins [26], venous congestion, and the increased intraocular pressure and consequent glaucoma injurious course [26]. For the BPC 157 therapy importance estimation [18,19[18][19][23][24][27][28][29][31][37][38][39][40],23,24,27,28,29,31,37,38,39,40], one remaining episcleral vein was upgraded so that BPC 157 therapy did compensate all functions; otherwise, inescapable venous congestion and the increased intraocular pressure and consequent glaucoma injurious course fully reversed [26]. Moreover, BPC 157 therapy (the rapid upgrading of the collateral pathways) has cured many severe syndromes, including multiorgan and vascular failure [18[18][19][23][24][27][28][29][31][37][38][39][40],19,23,24,27,28,29,31,37,38,39,40], and heart dysfunction and thrombosis as cause–consequence, in particular. Otherwise, without therapy, these syndromes were commonly presented in rats with the permanent occlusion of major vessels (veins and/or arteries [18,19,20,22[18][19][20][22][23][24][25][26][27][28][29][30],23,24,25,26,27,28,29,30], peripherally and centrally), major intoxication (lithium, alcohol) [39,40][39][40], acute pancreatitis [37], myocardial infarction [37], and maintained intra-abdominal hypertension [31]. Its applicability in the rapid upgrading of the collateral pathways may likely provide an additional beneficial effect for the heart functions, and various vessel tributaries, and normalization/attenuation of the intracranial (sinus sagittal) hypertension, portal and caval hypertension and aortal hypotension, and counteraction of the multiorgan failure syndrome [18,19,23,24,27,28,29,31,37,38,39,40][18][19][23][24][27][28][29][31][37][38][39][40].

References

  1. Savage, P.; Cox, B.; Linden, K.; Coburn, J.; Shahmohammadi, M.; Menown, I. Advances in clinical cardiology 2021: A summary of key clinical trials. Adv. Ther. 2022, 39, 2398–2437.
  2. Vukojevic, J.; Milavic, M.; Perovic, D.; Ilic, S.; Zemba Cilic, A.; Duran, N.; Strbe, S.; Zoricic, Z.; Filipcic, I.; Brecic, P.; et al. Pentadecapeptide BPC 157 and the central nervous system. Neural. Regen. Res. 2022, 17, 482–487.
  3. Seiwerth, S.; Milavic, M.; Vukojevic, J.; Gojkovic, S.; Krezic, I.; Vuletic, L.B.; Pavlov, K.H.; Petrovic, A.; Sikiric, S.; Vranes, H.; et al. Stable gastric pentadecapeptide BPC 157 and wound healing. Front. Pharmacol. 2021, 12, 627533.
  4. Sikiric, P.; Hahm, K.B.; Blagaic, A.B.; Tvrdeic, A.; Pavlov, K.H.; Petrovic, A.; Kokot, A.; Gojkovic, S.; Krezic, I.; Drmic, D.; et al. Stable gastric pentadecapeptide BPC 157, Robert’s stomach cytoprotection/adaptive cytoprotection/organoprotection, and Selye’s stress coping response: Progress, achievements, and the future. Gut Liver 2020, 14, 153–167.
  5. Park, J.M.; Lee, H.J.; Sikiric, P.; Hahm, K.B. BPC 157 rescued NSAID-cytotoxicity via stabilizing intestinal permeability and enhancing cytoprotection. Curr. Pharm. Des. 2020, 26, 2971–2981.
  6. Kang, E.A.; Han, Y.M.; An, J.M.; Park, Y.J.; Sikiric, P.; Kim, D.H.; Kwon, K.A.; Kim, Y.J.; Yang, D.; Tchah, H.; et al. BPC157 as potential agent rescuing from cancer cachexia. Curr. Pharm. Des. 2018, 24, 1947–1956.
  7. Sikiric, P.; Rucman, R.; Turkovic, B.; Sever, M.; Klicek, R.; Radic, B.; Drmic, D.; Stupnisek, M.; Misic, M.; Vuletic, L.B.; et al. Novel cytoprotective mediator, stable gastric pentadecapeptide BPC 157. Vascular recruitment and gastrointestinal tract healing. Curr. Pharm. Des. 2018, 24, 1990–2001.
  8. Sikiric, P.; Skrtic, A.; Gojkovic, S.; Krezic, I.; Zizek, H.; Lovric, E.; Sikiric, S.; Knezevic, M.; Strbe, S.; Milavic, M.; et al. Cytoprotective gastric pentadecapeptide BPC 157 resolves major vessel occlusion disturbances, ischemia-reperfusion injury following Pringle maneuver, and Budd-Chiari syndrome. World J. Gastroenterol. 2022, 28, 23–46.
  9. Deek, S.A. BPC 157 as potential treatment for COVID-19. Med. Hypotheses 2021, 158, 110736.
  10. Robert, A. Cytoprotection by prostaglandins. Gastroenterology 1979, 77, 761–767.
  11. Szabo, S. Mechanism of mucosal protection. In Gastric Cytoprotection: A Clinician’s Guide; Hollander, D., Tarnawski, A., Eds.; Plenum Medical Book Co.: New York, NY, USA, 1989; pp. 49–90.
  12. Szabo, S.; Trier, J.S.; Brown, A.; Schnoor, J. Early vascular injury and increased vascular permeability in gastric mucosal injury caused by ethanol in the rat. Gastroenterology 1985, 88, 228–236.
  13. Elliott, G.; Whited, B.A.; Purmalis, A.; Davis, J.P.; Field, S.O.; Lancaster, C.; Robert, A. Effect of 16,16-dimethyl PGE2 on renal papillary necrosis and gastrointestinal ulcerations (gastric, duodenal, intestinal) produced in rats by mefenamic acid. Life Sci. 1986, 39, 423–432.
  14. Robert, A.; Lum, J.T.; Lancaster, C.; Olafsson, A.S.; Kolbasa, K.P.; Nezamis, J.E. Prevention by prostaglandins of caerulein-induced pancreatitis in rats. Lab. Investig. 1989, 60, 677–691.
  15. Szabo, S. Experimental basis for a role for sulfhydryls and dopamine in ulcerogenesis: A primer for cytoprotection--organoprotection. Klin Wochenschr. 1986, 64 (Suppl. S7), 116–122.
  16. Szabó, S. Role of sulfhydryls and early vascular lesions in gastric mucosal injury. Acta Physiol. Hung. 1984, 64, 203–214.
  17. Szabo, S.; Usadel, K.H. Cytoprotection—Organoprotection by somatostatin: Gastric and hepatic lesions. Experientia 1982, 38, 254–256.
  18. Hrelec, M.; Klicek, R.; Brcic, L.; Brcic, I.; Cvjetko, I.; Seiwerth, S.; Sikiric, P. Abdominal aorta anastomosis in rats and stable gastric pentadecapeptide BPC 157, prophylaxis and therapy. J. Physiol. Pharmacol. 2009, 60 (Suppl. S7), 161–165.
  19. Knezevic, M.; Gojkovic, S.; Krezic, I.; Zizek, H.; Malekinusic, D.; Vrdoljak, B.; Vranes, H.; Knezevic, T.; Barisic, I.; Horvat Pavlov, K.; et al. 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. Biomedicines 2021, 9, 609.
  20. Vukojevic, J.; Vrdoljak, B.; Malekinusic, D.; Siroglavic, M.; Milavic, M.; Kolenc, D.; Boban Blagaic, A.; Bateljam, L.; Drmic, D.; Seiwerth, S.; et al. The effect of pentadecapeptide BPC 157 on hippocampal ischemia/reperfusion injuries in rats. Brain Behav. 2020, 10, e01726.
  21. Zlatar, M.; Kokot, A.; Vuletic, L.B.; Masnec, S.; Kralj, T.; Perisa, M.M.; Barisic, I.; Radic, B.; Milanovic, K.; Drmic, D.; et al. BPC 157 as a therapy for retinal ischemia induced by retrobulbar application of L-NAME in rats. Front. Pharmacol. 2021, 12, 632295.
  22. Vukojevic, J.; Siroglavic, M.; Kasnik, K.; Kralj, T.; Stancic, D.; Kokot, A.; Kolaric, D.; Drmic, D.; Sever, A.Z.; Barisic, I.; et al. Rat inferior caval vein (ICV) ligature and particular new insights with the stable gastric pentadecapeptide BPC 157. Vascul. Pharmacol. 2018, 106, 54–66.
  23. Gojkovic, S.; Krezic, I.; Vrdoljak, B.; Malekinusic, D.; Barisic, I.; Petrovic, A.; Horvat Pavlov, K.; Kolovrat, M.; Duzel, A.; Knezevic, M.; et al. Pentadecapeptide BPC 157 resolves suprahepatic occlusion of the inferior caval vein, Budd-Chiari syndrome model in rats. World J. Gastrointest. Pathophysiol. 2020, 11, 1–19.
  24. Knezevic, M.; Gojkovic, S.; Krezic, I.; Zizek, H.; Vranes, H.; Malekinusic, D.; Vrdoljak, B.; Knezevic, T.; Pavlov, K.H.; Drmic, D.; et al. Complex syndrome of the complete occlusion of the end of the superior mesenteric vein, opposed with the stable gastric pentadecapeptide BPC 157 in rats. Biomedicines 2021, 9, 1029.
  25. Amic, F.; Drmic, D.; Bilic, Z.; Krezic, I.; Zizek, H.; Peklic, M.; Klicek, R.; Pajtak, A.; Amic, E.; Vidovic, T.; et al. Bypassing major venous occlusion and duodenal lesions in rats, and therapy with the stable gastric pentadecapeptide BPC 157, L-NAME and L-arginine. World J. Gastroenterol. 2018, 24, 5366–5378.
  26. Kralj, T.; Kokot, A.; Zlatar, M.; Masnec, S.; Kasnik Kovac, K.; Milkovic Perisa, M.; Batelja Vuletic, L.; Giljanovic, A.; Strbe, S.; Sikiric, S.; et al. Stable gastric pentadecapeptide BPC 157 therapy of rat glaucoma. Biomedicines 2021, 10, 89.
  27. Gojkovic, S.; Krezic, I.; Vranes, H.; Zizek, H.; Drmic, D.; Pavlov, K.H.; Petrovic, A.; Batelja, L.; Milavic, M.; Sikiric, S.; et al. BPC 157 therapy and the permanent occlusion of the superior sagittal sinus in rat. Vascular recruitment. Biomedicines 2021, 9, 744.
  28. Kolovrat, M.; Gojkovic, S.; Krezic, I.; Malekinusic, D.; Vrdoljak, B.; Kasnik Kovac, K.; Kralj, T.; Drmic, D.; Barisic, I.; Horvat Pavlov, K.; et al. Pentadecapeptide BPC 157 resolves Pringle maneuver in rats, both ischemia and reperfusion. World J. Hepatol. 2020, 12, 184–206.
  29. Knezevic, M.; Gojkovic, S.; Krezic, I.; Zizek, H.; Malekinusic, D.; Vrdoljak, B.; Knezevic, T.; Vranes, H.; Drmic, D.; Staroveski, M.; et al. Occluded superior mesenteric artery and vein. Therapy with the stable gastric pentadecapeptide BPC 157. Biomedicines 2021, 9, 792.
  30. Duzel, A.; Vlainic, J.; Antunovic, M.; Malekinusic, D.; Vrdoljak, B.; Samara, M.; Gojkovic, S.; Krezic, I.; Vidovic, T.; Bilic, Z.; et al. Stable gastric pentadecapeptide BPC 157 in the treatment of colitis and ischemia and reperfusion in rats: New insights. World J. Gastroenterol. 2017, 23, 8465–8488.
  31. Tepes, M.; Gojkovic, S.; Krezic, I.; Zizek, H.; Madzar, Z.; Santak, G.; Batelja, L.; Milavic, M.; Sikiric, S.; Kocman, I.; et al. Stable gastric pentadecapeptide BPC 157 therapy for primary abdominal compartment syndrome in rats. Front. Pharmacol. 2021, 12, 718147.
  32. Drmic, D.; Samara, M.; Vidovic, T.; Malekinusic, D.; Antunovic, M.; Vrdoljak, B.; Ruzman, J.; Milkovic, P.M.; Horvat, K.P.; Jeyakumar, J.; et al. Counteraction of perforated cecum lesions in rats: Effects of pentadecapeptide BPC 157, L-NAME and L-arginine. World J. Gastroenterol. 2018, 24, 5462–5476.
  33. Bilic, Z.; Gojkovic, S.; Kalogjera, L.; Krezic, I.; Malekinusic, D.; Knezevic, M.; Sever, M.; Lojo, N.; Kokot, A.; Kasnik, K.; et al. Novel insight into Robert’s cytoprotection: Complex therapeutic effect of cytoprotective pentadecapeptide pentadecapeptide BPC 157 in rats with perforated stomach throughout modulation of nitric oxide-system. Comparison with L-arginine, ranitidine and pantoprazole therapy and L-NG-nitro-L-arginine methyl ester worsening. J. Physiol. Pharmacol. 2021, 72.
  34. Cesar, L.B.; Gojkovic, S.; Krezic, I.; Malekinusic, D.; Zizek, H.; Vuletic, L.B.; Petrovic, A.; Pavlov, K.H.; Drmic, D.; Kokot, A.; et al. Bowel adhesion and therapy with the stable gastric pentadecapeptide BPC 157, L-NAME and L-arginine in rats. World J. Gastrointest. Pharmacol. Ther. 2020, 11, 93–109.
  35. Perovic, D.; Kolenc, D.; Bilic, V.; Somun, N.; Drmic, D.; Elabjer, E.; Buljat, G.; Seiwerth, S.; Sikiric, P. Stable gastric pentadecapeptide BPC 157 can improve the healing course of spinal cord injury and lead to functional recovery in rats. J. Orthop. Surg. Res. 2019, 14, 199.
  36. Perovic, D.; Milavic, M.; Dokuzovic, S.; Krezic, I.; Gojkovic, S.; Vranes, H.; Bebek, I.; Bilic, V.; Somun, N.; Brizic, I.; et al. Novel therapeutic effects in rat spinal cord injuries: Recovery of the definitive and early spinal cord injury by the administration of pentadecapeptide BPC 157 therapy. Curr. Issues Mol. Biol. 2022, 44, 1901–1927.
  37. Smoday, I.M.; Petrovic, I.; Kalogjera, L.; Vranes, H.; Zizek, H.; Krezic, I.; Gojkovic, S.; Skorak, I.; Hriberski, K.; Brizic, I.; et al. Therapy effect of the stable gastric pentadecapeptide BPC 157 on acute pancreatitis as vascular failure-induced severe peripheral and central syndrome in rats. Biomedicines 2022, 10, 1299.
  38. Barisic, I.; Balenovic, D.; Udovicic, M.; Bardak, D.; Strinic, D.; Vlainic, J.; Vranes, H.; Smoday, I.M.; Krezic, I.; Milavic, M.; et al. Stable gastric pentadecapeptide BPC 157 may counteract myocardial infarction induced by isoprenaline in rats. Biomedicines 2022, 10, 265.
  39. Strbe, S.; Gojkovic, S.; Krezic, I.; Zizek, H.; Vranes, H.; Barisic, I.; Strinic, D.; Orct, T.; Vukojevic, J.; Ilic, S.; et al. Over-dose lithium toxicity as an occlusive-like syndrome in rats and gastric pentadecapeptide BPC 157. Biomedicines 2021, 9, 1506.
  40. Gojkovic, S.; Krezic, I.; Vranes, H.; Zizek, H.; Drmic, D.; Batelja Vuletic, L.; Milavic, M.; Sikiric, S.; Stilinovic, I.; Simeon, P.; et al. Robert’s intragastric alcohol-induced gastric lesion model as an escalated general peripheral and central syndrome, counteracted by the stable gastric pentadecapeptide BPC 157. Biomedicines 2021, 9, 1300.
  41. Udovicic, M.; Sever, M.; Kavur, L.; Loncaric, K.; Barisic, I.; Balenovic, D.; Zivanovic Posilovic, G.; Strinic, D.; Uzun, S.; Batelja Vuletic, L.; et al. Stable gastric pentadecapeptide BPC 157 therapy for monocrotaline-induced pulmonary hypertension in rats leads to prevention and reversal. Biomedicines 2021, 9, 822.
  42. Loosen, S.H.; Roderburg, C.; Curth, O.; Gaensbacher, J.; Joerdens, M.; Luedde, T.; Konrad, M.; Kostev, K.; Luedde, M. The spectrum of comorbidities at the initial diagnosis of heart failure a case control study. Sci. Rep. 2022, 12, 2670.
  43. Lawson, C.A.; Testani, J.M.; Mamas, M.; Damman, K.; Jones, P.W.; Teece, L.; Kadam, U.T. Chronic kidney disease, worsening renal function and outcomes in a heart failure community setting: A UK national study. Int. J. Cardiol. 2018, 267, 120–127.
  44. Lawson, C.A.; Solis-Trapala, I.; Dahlstrom, U.; Mamas, M.; Jaarsma, T.; Kadam, U.T.; Stromberg, A. Comorbidity health pathways in heart failure patients: A sequences-of-regressions analysis using cross-sectional data from 10,575 patients in the Swedish Heart Failure Registry. PLoS Med. 2018, 15, e1002540.
  45. Hubich, A.I.; Bondar, A.Y.; Kastsiuk, T.U.; Kastsiuk, U.A.; Lakhvich, F.A.; Sholukh, M.V. Hepatoprotective action of prostaglandin A(2) analogs under CCl(4)-induced liver injury in vitro. Hepatol. Res. 2007, 37, 416–424.
  46. Vincenti, F.; Goldberg, L.I. Combined use of dopamine and prostaglandin A1 in patients with acute renal failure and hepatorenal syndrome. Prostaglandins. 1978, 15, 463–472.
  47. Takakuma, A.; Nishii, M.; Valaperti, A.; Hiraga, H.; Saji, R.; Sakai, K.; Matsumura, R.; Miyata, Y.; Oba, N.; Nunose, F.; et al. Prostaglandin-E2 receptor-4 stimulant rescues cardiac malfunction during myocarditis and protects the heart from adverse ventricular remodeling after myocarditis. Sci. Rep. 2021, 11, 20961.
  48. Tudor, M.; Jandric, I.; Marovic, A.; Gjurasin, M.; Perovic, D.; Radic, B.; Blagaic, A.B.; Kolenc, D.; Brcic, L.; Zarkovic, K.; et al. Traumatic brain injury in mice and pentadecapeptide BPC 157 effect. Regul Pept. 2010, 160, 26–32.
  49. Lovric-Bencic, M.; Sikiric, P.; Hanzevacki, J.S.; Seiwerth, S.; Rogic, D.; Kusec, V.; Aralica, G.; Konjevoda, P.; Batelja, L.; Blagaic, A.B. Doxorubicine-congestive heart failure-increased big endothelin-1 plasma concentration: Reversal by amlodipine, losartan, and gastric pentadecapeptide BPC157 in rat and mouse. J. Pharmacol. Sci. 2004, 95, 19–26.
  50. Stancic-Rokotov, D.; Slobodnjak, Z.; Aralica, J.; Aralica, G.; Perovic, D.; Staresinic, M.; Gjurasin, M.; Anic, T.; Zoricic, I.; Buljat, G.; et al. Lung lesions and anti-ulcer agents beneficial effect: Anti-ulcer agents pentadecapeptide BPC 157, ranitidine, omeprazole and atropine ameliorate lung lesion in rats. J. Physiol. Paris 2001, 95, 303–308.
  51. Grabarevic, Z.; Tisljar, M.; Artukovic, B.; Bratulic, M.; Dzaja, P.; Seiwerth, S.; Sikiric, P.; Peric, J.; Geres, D.; Kos, J. The influence of BPC 157 on nitric oxide agonist and antagonist induced lesions in broiler chicken. J. Physiol. Paris 1997, 91, 139–149.
  52. Stancic-Rokotov, D.; Sikiric, P.; Seiwerth, S.; Slobodnjak, Z.; Aralica, J.; Aralica, G.; Perovic, D.; Anic, T.; Zoricic, I.; Buljat, G.; et al. Ethanol gastric lesion aggravated by lung injury in rat. Therapy effect of antiulcer agents. J. Physiol. Paris 2001, 95, 289–293.
  53. Sikiric, P.; Seiwerth, S.; Grabarevic, Z.; Rucman, R.; Petek, M.; Rotkvic, I.; Turkovic, B.; Jagic, V.; Mildner, B.; Duvnjak, M.; et al. Hepatoprotective effect of BPC 157, a 15-amino acid peptide, on liver lesions induced by either restraint stress or bile duct and hepatic artery ligation or CCl4 administration. A comparative study with dopamine agonists and somatostatin. Life Sci. 1993, 53, PL291–PL296.
  54. Prkacin, I.; Separovic, J.; Aralica, G.; Perovic, D.; Gjurasin, M.; Lovric-Bencic, M.; Stancic-Rokotov, D.; Staresinic, M.; Anic, T.; Mikus, D.; et al. Portal hypertension and liver lesions in chronically alcohol drinking rats prevented and reversed by stable gastric pentadecapeptide BPC 157 (PL-10, PLD-116), and propranolol, but not ranitidine. J. Physiol. Paris 2001, 95, 315–324.
  55. Sever, A.Z.; Sever, M.; Vidovic, T.; Lojo, N.; Kolenc, D.; Vuletic, L.B.; Drmic, D.; Kokot, A.; Zoricic, I.; Coric, M.; et al. Stable gastric pentadecapeptide BPC 157 in the therapy of the rats with bile duct ligation. Eur. J. Pharmacol. 2019, 847, 130–142.
  56. Ilic, S.; Drmic, D.; Zarkovic, K.; Kolenc, D.; Coric, M.; Brcic, L.; Klicek, R.; Radic, B.; Sever, M.; Djuzel, V.; et al. High hepatotoxic dose of paracetamol produces generalized convulsions and brain damage in rats. A counteraction with the stable gastric pentadecapeptide BPC 157 (PL 14736). J. Physiol. Pharmacol. 2010, 61, 241–250.
  57. Drmic, D.; Kolenc, D.; Ilic, S.; Bauk, L.; Sever, M.; Zenko Sever, A.; Luetic, K.; Suran, J.; Seiwerth, S.; Sikiric, P. Celecoxib-induced gastrointestinal, liver and brain lesions in rats, counteraction by BPC 157 or L-arginine, aggravation by L-NAME. World J. Gastroenterol. 2017, 23, 5304–5312.
  58. Lojo, N.; Rasic, Z.; Sever, A.Z.; Kolenc, D.; Vukusic, D.; Drmic, D.; Zoricic, I.; Sever, M.; Seiwerth, S.; Sikiric, P. Effects of diclofenac, L-NAME, L-arginine, and pentadecapeptide BPC157 on gastrointestinal, liver, and brain lesions, failed anastomosis, and intestinal adaptation deterioration in 24 h-short-bowel rats. PLoS ONE 2016, 11, e0162590.
  59. Ilic, S.; Drmic, D.; Zarkovic, K.; Kolenc, D.; Brcic, L.; Radic, B.; Djuzel, V.; Blagaic, A.B.; Romic, Z.; Dzidic, S.; et al. Ibuprofen hepatic encephalopathy, hepatomegaly, gastric lesion and gastric pentadecapeptide BPC 157 in rats. Eur. J. Pharmacol. 2011, 667, 322–329.
  60. Ilic, S.; Drmic, D.; Franjic, S.; Kolenc, D.; Coric, M.; Brcic, L.; Klicek, R.; Radic, B.; Sever, M.; Djuzel, V.; et al. Pentadecapeptide BPC 157 and its effects on a NSAID toxicity model: Diclofenac-induced gastrointestinal, liver, and encephalopathy lesions. Life Sci. 2011, 88, 535–542.
  61. Ilic, S.; Brcic, I.; Mester, M.; Filipovicm, M.; Sever, M.; Klicek, R.; Barisic, I.; Radic, B.; Zoricic, Z.; Bilic, V.; et al. Over-dose insulin and stable gastric pentadecapeptide BPC 157: Attenuated gastric ulcers, seizures, brain lesions, hepatomegaly, fatty liver, breakdown of liver glycogen, profound hypoglycemia and calcification in rats. J. Physiol. Pharmacol. 2009, 60, 107–114.
  62. Vranes, H.; Krezic, I.; Gojkovic, S.; Zizek, H.; Durasin, T.; Petrovic, A.; Horvat Pavlov, K.; Batelja, L.; Blagaic Boban, A.; Seiwerth, S.; et al. In hydornephrosis-rats, BPC 157 exerts a strong anti-ulcer effect in both stomach and duodenum along with marked kidney recovery. FASEB J. 2020, 34 (Suppl. S1), 1.
  63. Drmic, D.; Sucic, M.; Zenko Sever, A.; Kolenc, D.; Suran, J.; Seiwerth, S.; Sikiric, P. BPC 157 counteracts gastric lesions after bilateral nephrectomy and attenuates deleterious course in rats. FASEB J. 2015, 29 (Suppl. S1), 628.10.
  64. Drmic, D.; Sucic, M.; Zenko Sever, A.; Kolenc, D.; Andrijasevic, V.; Suran, J.; Seiwerth, S.; Sikiric, P. Attenuation of the deleterious couse and gastric lesions after bilateral nephrectomy in rats, NO-system relation. BPC 157, L-arginine, L-NAME. FASEB J. 2016, 30 (Suppl. S1), 720.2.
  65. Sikirić, P.; Seiwerth, S.; Grabarević, Z.; Rucman, R.; Petek, M.; Jagić, V.; Turković, B.; Rotkvić, I.; Mise, S.; Zoricić, I.; et al. Salutary and prophylactic effect of pentadecapeptide BPC 157 on acute pancreatitis and concomitant gastroduodenal lesions in rats. Dig. Dis. Sci. 1996, 41, 1518–1526.
  66. Petrovic, I.; Dobric, I.; Drmic, D.; Sever, M.; Klicek, R.; Radic, B.; Brcic, L.; Kolenc, D.; Zlatar, M.; Kunjko, K.; et al. BPC 157 therapy to detriment sphincters failure-esophagitis-pancreatitis in rat and acute pancreatitis patients low sphincters pressure. J. Physiol. Pharmacol. 2011, 62, 527–534.
  67. Seiwerth, S.; Rucman, R.; Turkovic, B.; Sever, M.; Klicek, R.; Radic, B.; Drmic, D.; Stupnisek, M.; Misic, M.; Vuletic, L.B.; et al. BPC 157 and standard angiogenic growth factors. Gastrointestinal tract healing, lessons from tendon, ligament, muscle and bone healing. Curr. Pharm. Des. 2018, 24, 1972–1989.
  68. Hsieh, M.J.; Lee, C.H.; Chueh, H.Y.; Chang, G.J.; Huang, H.Y.; Lin, Y.; Pang, J.S. Modulatory effects of BPC 157 on vasomotor tone and the activation of Src-Caveolin-1-endothelial nitric oxide synthase pathway. Sci. Rep. 2020, 10, 17078.
  69. Tkalcevic, V.I.; Cuzic, S.; Brajsa, K.; Mildner, B.; Bokulic, A.; Situm, K.; Perovic, D.; Glojnaric, I.; Parnham, M.J. Enhancement by PL 14736 of granulation and collagen organization in healing wounds and the potential role of egr-1 expression. Eur. J. Pharmacol. 2007, 570, 212–221.
  70. Bilic, M.; Bumber, Z.; Blagaic, A.B.; Batelja, L.; Seiwerth, S.; Sikiric, P. The stable gastric pentadecapeptide BPC 157, given locally, improves CO2 laser healing in mice. Burns 2005, 31, 310–315.
  71. Sikiric, P.; Seiwerth, S.; Mise, S.; Staresinic, M.; Bedekovic, V.; Zarkovic, N.; Borovic, S.; Gjurasin, M.; Boban-Blagaic, A.; Batelja, L.; et al. Corticosteroid-impairment of healing and gastric pentadecapeptide BPC-157 creams in burned mice. Burns 2003, 29, 323–334.
  72. Mikus, D.; Sikiric, P.; Seiwerth, S.; Petricevic, A.; Aralica, G.; Druzijancic, N.; Rucman, R.; Petek, M.; Pigac, B.; Perovic, D.; et al. Pentadecapeptide BPC 157 cream improves burn-wound healing and attenuates burn-gastric lesions in mice. Burns 2001, 27, 817–827.
  73. Gjurasin, M.; Miklic, P.; Zupancic, B.; Perovic, D.; Zarkovic, K.; Brcic, L.; Kolenc, D.; Radic, B.; Seiwerth, S.; Sikiric, P. Peptide therapy with pentadecapeptide BPC 157 in traumatic nerve injury. Regul. Pept. 2010, 160, 33–41.
  74. Chang, C.H.; Tsai, W.C.; Lin, M.S.; Hsu, Y.H.; Pang, J.H.S. The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration. J. Appl. Physiol. 2011, 110, 774–780.
  75. Chang, C.H.; Tsai, W.C.; Hsu, Y.H.; Pang, J.H.S. Pentadecapeptide BPC 157 enhances the growth hormone receptor expression in tendon fibroblasts. Molecules 2014, 19, 19066–19077.
  76. Staresinic, M.; Sebecic, B.; Patrlj, L.; Jadrijevic, S.; Suknaic, S.; Perovic, D.; Aralica, G.; Zarkovic, N.; Borovic, S.; Srdjak, M.; et al. Gastric pentadecapeptide BPC 157 accelerates healing of transected rat Achilles tendon and in vitro stimulates tendocytes growth. J. Orthop. Res. 2003, 21, 976–983.
  77. Krivic, A.; Anic, T.; Seiwerth, S.; Huljev, D.; Sikiric, P. Achilles detachment in rat and stable gastric pentadecapeptide BPC 157: Promoted tendon-to-bone healing and opposed corticosteroid aggravation. J. Orthop. Res. 2006, 24, 982–989.
  78. Krivic, A.; Majerovic, M.; Jelic, I.; Seiwerth, S.; Sikiric, P. Modulation of early functional recovery of Achilles tendon to bone unit after transection by BPC 157 and methylprednisolone. Inflamm. Res. 2008, 57, 205–210.
  79. Brcic, L.; Brcic, I.; Staresinic, M.; Novinscak, T.; Sikiric, P.; Seiwerth, S. Modulatory effect of gastric pentadecapeptide BPC 157 on angiogenesis in muscle and tendon healing. J. Physiol. Pharmacol. 2009, 60, 191–196.
  80. Japjec, M.; Horvat Pavlov, K.; Petrovic, A.; Staresinic, M.; Sebecic, B.; Buljan, M.; Vranes, H.; Giljanovic, A.; Drmic, D.; Japjec, M.; et al. Stable Gastric Pentadecapeptide BPC 157 as a therapy for the disable myotendinous junctions in rats. Biomedicines 2021, 9, 1547.
  81. Staresinic, M.; Petrovic, I.; Novinscak, T.; Jukic, I.; Pevec, D.; Suknaic, S.; Kokic, N.; Batelja, L.; Brcic, L.; Boban-Blagaic, A.; et al. Effective therapy of transected quadriceps muscle in rat: Gastric pentadecapeptide BPC 157. J. Orthop. Res. 2006, 24, 1109–1117.
  82. Novinscak, T.; Brcic, L.; Staresinic, M.; Jukic, I.; Radic, B.; Pevec, D.; Mise, S.; Tomasovic, S.; Brcic, I.; Banic, T.; et al. Gastric pentadecapeptide BPC 157 as an effective therapy for muscle crush injury in the rat. Surg. Today 2008, 38, 716–725.
  83. Pevec, D.; Novinscak, T.; Brcic, L.; Sipos, K.; Jukic, I.; Staresinic, M.; Mise, S.; Brcic, I.; Kolenc, D.; Klicek, R.; et al. Impact of pentadecapeptide BPC 157 on muscle healing impaired by systemic corticosteroid application. Med. Sci. Monit. 2010, 16, 81–88.
  84. Mihovil, I.; Radic, B.; Brcic, L.; Brcic, I.; Vukoja, I.; Ilic, S.; Boban Blagaic, A.; Seiwerth, S.; Sikiric, P. Beneficial effect of pentadecapeptide BPC 157 on denervated muscle in rats. J. Physiol. Pharmacol. 2009, 60, 69.
  85. Cerovecki, T.; Bojanic, I.; Brcic, L.; Radic, B.; Vukoja, I.; Seiwerth, S.; Sikiric, P. Pentadecapeptide BPC 157 (PL 14736) improves ligament healing in the rat. J. Orthop. Res. 2010, 28, 1155–1161.
  86. Sebecic, B.; Nikolic, V.; Sikiric, P.; Seiwerth, S.; Sosa, T.; Patrlj, L.; Grabarević, Z.; Rucman, R.; Petek, M.; Konjevoda, P.; et al. Osteogenic effect of a gastric pentadecapeptide BPC 157, on the healing of segmental bone defect in rabbits. A comparison with bone marrow and autologous cortical bone implantation. Bone 1999, 24, 195–202.
  87. Keremi, B.; Lohinai, Z.; Komora, P.; Duhaj, S.; Borsi, K.; Jobbagy-Ovari, G.; Kallo, K.; Szekely, A.D.; Fazekas, A.; Dobo-Nagy, C.; et al. Antiinflammatory effect of BPC 157 on experimental periodontitis in rats. J. Physiol. Pharmacol. 2009, 60 (Suppl. S7), 115–122.
  88. Gamulin, O.; Serec, K.; Bilic, V.; Balarin, M.; Kosovic, M.; Drmic, D.; Brcic, L.; Seiwerth, S.; Sikiric, P. Monitoring the healing process of rat bones using Raman spectroscopy. J. Mol. Struct. 2013, 1044, 303–313.
  89. Stambolija, V.; Stambolija, T.P.; Holjevac, J.K.; Murselovic, T.; Radonic, J.; Duzel, V.; Duplancic, B.; Uzun, S.; Zivanovic-Posilovic, G.; Kolenc, D.; et al. BPC 157: The counteraction of succinylcholine, hyperkalemia, and arrhythmias. Eur. J. Pharmacol. 2016, 781, 83–91.
  90. Sikiric, P.; Drmic, D.; Sever, M.; Klicek, R.; Blagaic, A.B.; Tvrdeic, A.; Kralj, T.; Kovac, K.K.; Vukojevic, J.; Siroglavic, M.; et al. Fistulas healing. Stable gastric pentadecapeptide BPC 157 therapy. Curr. Pharm. Des. 2020, 26, 2991–3000.
  91. Stupnisek, M.; Franjic, S.; Drmic, D.; Hrelec, M.; Kolenc, D.; Radic, B.; Bojic, D.; Vcev, A.; Seiwerth, S.; Sikiric, P. Pentadecapeptide BPC 157 reduces bleeding time and thrombocytopenia after amputation in rats treated with heparin, warfarin or aspirin. Thromb. Res. 2012, 129, 652–659.
  92. Szekeres, L. Pharmacological induction of delayed and prolonged cardiac protection: The role of prostanoids. Exp. Clin. Cardiol. 2004, 9, 7–12.
  93. Szekeres, L. Cardioprotection by anti-ischaemic and cytoprotective drugs. Basic Res. Cardiol. 1987, 82 (Suppl. S2), 325–333.
  94. Szekeres, L.; Pataricza, J.; Szilvássy, Z.; Udvary, E.; Végh, A. Cardioprotection: Endogenous protective mechanisms promoted by prostacyclin. Basic Res. Cardiol. 1991, 86 (Suppl. S3), 215–221.
  95. Masnec, S.; Kokot, A.; Zlatar, M.; Kalauz, M.; Kunjko, K.; Radic, B.; Klicek, R.; Drmic, D.; Lazic, R.; Brcic, L.; et al. Perforating corneal injury in rat and pentadecapeptide BPC 157. Exp. Eye Res. 2015, 136, 9–15.
More
Video Production Service