BPC 157 Rescued NSAID-cytotoxicity Via Stabilizing Intestinal Permeability and Enhancing Cytoprotection

Page: [2971 - 2981] Pages: 11

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Abstract

The stable gastric pentadecapeptide BPC 157 protects stomach cells, maintains gastric integrity against various noxious agents such as alcohol, nonsteroidal anti-inflammatory drugs (NSAIDs), and exerts cytoprotection/ adaptive cytoprotection/organoprotection in other epithelia, that is, skin, liver, pancreas, heart, and brain. Especially BPC 157 counteracts gastric endothelial injury that precedes and induces damage to the gastric epithelium and generalizes "gastric endothelial protection" to protection of the endothelium of other vessels including thrombosis, prolonged bleeding, and thrombocytopenia. In this background, we put the importance of BPC 157 as a possible way of securing GI safety against NSAIDs-induced gastroenteropathy since still unmet medical needs to mitigate NSAIDs-induced cytotoxicity are urgent. Furthermore, gastrointestinal irritants such as physical or mental stress, NSAIDs administration, surfactants destroyer such as bile acids, alcohol can lead to leaky gut syndrome through increasing epithelial permeability. In this review article, we described the potential rescuing actions of BPC 157 against leaky gut syndrome after NSAIDs administration for the first time.

Keywords: BPC 157, gut permeability, NSAID induced gastroenteropathy, leaky gut syndrome, epithelial permeability, bile acids.

[1]
Camilleri M. Leaky gut: mechanisms, measurement and clinical implications in humans. Gut 2019; 68(8): 1516-26.
[http://dx.doi.org/10.1136/gutjnl-2019-318427] [PMID: 31076401]
[2]
Quigley EM, Spiller RC. Constipation and the Microbiome: Lumen Versus Mucosa! Gastroenterology 2016; 150(2): 300-3.
[http://dx.doi.org/10.1053/j.gastro.2015.12.023] [PMID: 26710987]
[3]
Obrenovich MEM. Leaky Gut, Leaky Brain? Microorganisms 2018; 6(4): 6.
[http://dx.doi.org/10.3390/microorganisms6040107] [PMID: 30340384]
[4]
Konturek PC, Harsch IA, Konturek K, et al. Gut−Liver Axis: How Do Gut Bacteria Influence the Liver? Med Sci (Basel) 2018; 6(3): 6.
[http://dx.doi.org/10.3390/medsci6030079] [PMID: 30227645]
[5]
Fändriks L. Roles of the gut in the metabolic syndrome: an overview. J Intern Med 2017; 281(4): 319-36.
[http://dx.doi.org/10.1111/joim.12584] [PMID: 27991713]
[6]
Anderson G, Seo M, Berk M, Carvalho AF, Maes M. Gut Permeability and Microbiota in Parkinson’s Disease: Role of Depression, Tryptophan Catabolites, Oxidative and Nitrosative Stress and Melatonergic Pathways. Curr Pharm Des 2016; 22(40): 6142-51.
[http://dx.doi.org/10.2174/1381612822666160906161513] [PMID: 27604608]
[7]
Li X, Atkinson MA. The role for gut permeability in the pathogenesis of type 1 diabetes-a solid or leaky concept? Pediatr Diabetes 2015; 16(7): 485-92.
[http://dx.doi.org/10.1111/pedi.12305] [PMID: 26269193]
[8]
Lau WL, Kalantar-Zadeh K, Vaziri ND. The Gut as a Source of Inflammation in Chronic Kidney Disease. Nephron 2015; 130(2): 92-8.
[http://dx.doi.org/10.1159/000381990] [PMID: 25967288]
[9]
Gupta H, Youn GS, Shin MJ, Suk KT. Role of Gut Microbiota in Hepatocarcinogenesis. Microorganisms 2019; 7(5): 7.
[http://dx.doi.org/10.3390/microorganisms7050121] [PMID: 31060311]
[10]
Saggioro A. Leaky gut, microbiota, and cancer: an incoming hypothesis. J Clin Gastroenterol 2014; 48(Suppl. 1): S62-6.
[http://dx.doi.org/10.1097/MCG.0000000000000255] [PMID: 25291131]
[11]
Meijers B, Jouret F, Evenepoel P. Linking gut microbiota to cardiovascular disease and hypertension: Lessons from chronic kidney disease. Pharmacol Res 2018; 133: 101-7.
[http://dx.doi.org/10.1016/j.phrs.2018.04.023] [PMID: 29715498]
[12]
Bhatt AP, Gunasekara DB, Speer J, et al. Nonsteroidal Anti-Inflammatory Drug-Induced Leaky Gut Modeled Using Polarized Monolayers of Primary Human Intestinal Epithelial Cells. ACS Infect Dis 2018; 4(1): 46-52.
[http://dx.doi.org/10.1021/acsinfecdis.7b00139] [PMID: 29094594]
[13]
Kwak DS, Lee OY, Lee KN, et al. The Effect of DA-6034 on Intestinal Permeability in an Indomethacin-Induced Small Intestinal Injury Model. Gut Liver 2016; 10(3): 406-11.
[http://dx.doi.org/10.5009/gnl15251] [PMID: 27114435]
[14]
Bjarnason I, Scarpignato C, Holmgren E, Olszewski M, Rainsford KD, Lanas A. Mechanisms of Damage to the Gastrointestinal Tract From Nonsteroidal Anti-Inflammatory Drugs. Gastroenterology 2018; 154(3): 500-14.
[http://dx.doi.org/10.1053/j.gastro.2017.10.049] [PMID: 29221664]
[15]
Han YM, Park JM, Kang JX, et al. Mitigation of indomethacin-induced gastrointestinal damages in fat-1 transgenic mice via gate-keeper action of ω-3-polyunsaturated fatty acids. Sci Rep 2016; 6: 33992.
[http://dx.doi.org/10.1038/srep33992] [PMID: 27658533]
[16]
Utzeri E, Usai P. Role of non-steroidal anti-inflammatory drugs on intestinal permeability and nonalcoholic fatty liver disease. World J Gastroenterol 2017; 23(22): 3954-63.
[http://dx.doi.org/10.3748/wjg.v23.i22.3954] [PMID: 28652650]
[17]
Rahman K, Desai C, Iyer SS, et al. Loss of Junctional Adhesion Molecule A Promotes Severe Steatohepatitis in Mice on a Diet High in Saturated Fat, Fructose, and Cholesterol. Gastroenterology 2016; 151: 733-46.
[18]
Lepage D, Bélanger É, Jones C, et al. Gata4 is critical to maintain gut barrier function and mucosal integrity following epithelial injury. Sci Rep 2016; 6: 36776.
[http://dx.doi.org/10.1038/srep36776] [PMID: 27827449]
[19]
Lee HJ, Han YM, An JM, et al. Role of omega-3 polyunsaturated fatty acids in preventing gastrointestinal cancers: current status and future perspectives. Expert Rev Anticancer Ther 2018; 18(12): 1189-203.
[http://dx.doi.org/10.1080/14737140.2018.1524299] [PMID: 30220238]
[20]
Yum HW, Kang JX, Hahm KB, Surh YJ. Constitutive ω-3 fatty acid production in fat-1 transgenic mice and docosahexaenoic acid administration to wild type mice protect against 2,4,6-trinitrobenzene sulfonic acid-induced colitis. Biochem Biophys Res Commun 2017; 487(4): 847-55.
[http://dx.doi.org/10.1016/j.bbrc.2017.04.140] [PMID: 28456627]
[21]
Tsukita S, Furuse M, Itoh M. Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol 2001; 2(4): 285-93.
[http://dx.doi.org/10.1038/35067088] [PMID: 11283726]
[22]
Turner JR. Intestinal mucosal barrier function in health and disease. Nat Rev Immunol 2009; 9(11): 799-809.
[http://dx.doi.org/10.1038/nri2653] [PMID: 19855405]
[23]
Stevenson BR, Siliciano JD, Mooseker MS, Goodenough DA. Identification of ZO-1: a high molecular weight polypeptide associated with the tight junction (zonula occludens) in a variety of epithelia. J Cell Biol 1986; 103(3): 755-66.
[http://dx.doi.org/10.1083/jcb.103.3.755] [PMID: 3528172]
[24]
Kimura Y, Shiozaki H, Hirao M, et al. Expression of occludin, tight-junction-associated protein, in human digestive tract. Am J Pathol 1997; 151(1): 45-54.
[PMID: 9212730]
[25]
Furuse M, Hirase T, Itoh M, et al. Occludin: a novel integral membrane protein localizing at tight junctions. J Cell Biol 1993; 123(6 Pt 2): 1777-88.
[http://dx.doi.org/10.1083/jcb.123.6.1777] [PMID: 8276896]
[26]
Chen Y, Merzdorf C, Paul DL, Goodenough DA. COOH terminus of occludin is required for tight junction barrier function in early Xenopus embryos. J Cell Biol 1997; 138(4): 891-9.
[http://dx.doi.org/10.1083/jcb.138.4.891] [PMID: 9265654]
[27]
Saitou M, Furuse M, Sasaki H, et al. Complex phenotype of mice lacking occludin, a component of tight junction strands. Mol Biol Cell 2000; 11(12): 4131-42.
[http://dx.doi.org/10.1091/mbc.11.12.4131] [PMID: 11102513]
[28]
Furuse M, Fujita K, Hiiragi T, Fujimoto K, Tsukita S. Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J Cell Biol 1998; 141(7): 1539-50.
[http://dx.doi.org/10.1083/jcb.141.7.1539] [PMID: 9647647]
[29]
Chiba H, Osanai M, Murata M, Kojima T, Sawada N. Transmembrane proteins of tight junctions. Biochim Biophys Acta 2008; 1778(3): 588-600.
[http://dx.doi.org/10.1016/j.bbamem.2007.08.017] [PMID: 17916321]
[30]
Mankertz J, Schulzke JD. Altered permeability in inflammatory bowel disease: pathophysiology and clinical implications. Curr Opin Gastroenterol 2007; 23(4): 379-83.
[http://dx.doi.org/10.1097/MOG.0b013e32816aa392] [PMID: 17545772]
[31]
Tamura A, Tsukita S. Paracellular barrier and channel functions of TJ claudins in organizing biological systems: advances in the field of barriology revealed in knockout mice. Semin Cell Dev Biol 2014; 36: 177-85.
[http://dx.doi.org/10.1016/j.semcdb.2014.09.019] [PMID: 25305579]
[32]
Van Itallie CM, Anderson JM. Claudins and epithelial paracellular transport. Annu Rev Physiol 2006; 68: 403-29.
[http://dx.doi.org/10.1146/annurev.physiol.68.040104.131404] [PMID: 16460278]
[33]
Suzuki T. Regulation of intestinal epithelial permeability by tight junctions. Cell Mol Life Sci 2013; 70(4): 631-59.
[http://dx.doi.org/10.1007/s00018-012-1070-x] [PMID: 22782113]
[34]
Nunbhakdi-Craig V, Machleidt T, Ogris E, Bellotto D, White CL III, Sontag E. Protein phosphatase 2A associates with and regulates atypical PKC and the epithelial tight junction complex. J Cell Biol 2002; 158(5): 967-78.
[http://dx.doi.org/10.1083/jcb.200206114] [PMID: 12196510]
[35]
Van Itallie CM, Tietgens AJ, LoGrande K, Aponte A, Gucek M, Anderson JM. Phosphorylation of claudin-2 on serine 208 promotes membrane retention and reduces trafficking to lysosomes. J Cell Sci 2012; 125(Pt 20): 4902-12.
[http://dx.doi.org/10.1242/jcs.111237] [PMID: 22825868]
[36]
Martìn-Padura I, Lostaglio S, Schneemann M, et al. Junctional adhesion molecule, a novel member of the immunoglobulin superfamily that distributes at intercellular junctions and modulates monocyte transmigration. J Cell Biol 1998; 142(1): 117-27.
[http://dx.doi.org/10.1083/jcb.142.1.117] [PMID: 9660867]
[37]
Garrido-Urbani S, Bradfield PF, Imhof BA. Tight junction dynamics: the role of junctional adhesion molecules (JAMs). Cell Tissue Res 2014; 355(3): 701-15.
[http://dx.doi.org/10.1007/s00441-014-1820-1] [PMID: 24595739]
[38]
Itoh M, Furuse M, Morita K, Kubota K, Saitou M, Tsukita S. Direct binding of three tight junction-associated MAGUKs, ZO-1, ZO-2, and ZO-3, with the COOH termini of claudins. J Cell Biol 1999; 147(6): 1351-63.
[http://dx.doi.org/10.1083/jcb.147.6.1351] [PMID: 10601346]
[39]
Haskins J, Gu L, Wittchen ES, Hibbard J, Stevenson BR. ZO-3, a novel member of the MAGUK protein family found at the tight junction, interacts with ZO-1 and occludin. J Cell Biol 1998; 141(1): 199-208.
[http://dx.doi.org/10.1083/jcb.141.1.199] [PMID: 9531559]
[40]
Willott E, Balda MS, Fanning AS, Jameson B, Van Itallie C, Anderson JM. The tight junction protein ZO-1 is homologous to the Drosophila discs-large tumor suppressor protein of septate junctions. Proc Natl Acad Sci USA 1993; 90(16): 7834-8.
[http://dx.doi.org/10.1073/pnas.90.16.7834] [PMID: 8395056]
[41]
Wang J, Ghosh SS, Ghosh S. Curcumin improves intestinal barrier function: modulation of intracellular signaling, and organization of tight junctions. Am J Physiol Cell Physiol 2017; 312(4): C438-45.
[http://dx.doi.org/10.1152/ajpcell.00235.2016] [PMID: 28249988]
[42]
Thakre-Nighot M, Blikslager AT. Indomethacin induces increase in gastric epithelial tight junction permeability via redistribution of occludin and activation of p38 MAPK in MKN-28 Cells. Tissue Barriers 2016; 4(3)e1187325
[http://dx.doi.org/10.1080/21688370.2016.1187325] [PMID: 27583191]
[43]
Wu HL, Gao X, Jiang ZD, et al. Attenuated expression of the tight junction proteins is involved in clopidogrel-induced gastric injury through p38 MAPK activation. Toxicology 2013; 304: 41-8.
[http://dx.doi.org/10.1016/j.tox.2012.11.020] [PMID: 23220562]
[44]
Oshima T, Miwa H, Joh T. Aspirin induces gastric epithelial barrier dysfunction by activating p38 MAPK via claudin-7. Am J Physiol Cell Physiol 2008; 295(3): C800-6.
[http://dx.doi.org/10.1152/ajpcell.00157.2008] [PMID: 18667601]
[45]
Shigetomi K, Ikenouchi J. Regulation of the epithelial barrier by post-translational modifications of tight junction membrane proteins. J Biochem 2018; 163(4): 265-72.
[http://dx.doi.org/10.1093/jb/mvx077] [PMID: 29186552]
[46]
Zhang L, Liu G, Han X, et al. Inhibition of p38 MAPK activation attenuates esophageal mucosal damage in a chronic model of reflux esophagitis. Neurogastroenterol Motil 2015; 27(11): 1648-56.
[http://dx.doi.org/10.1111/nmo.12664] [PMID: 26353842]
[47]
Shi S, Wang H, Gao H, et al. Increased gap density predicts weakness of the epithelial barrier in vivo by confocal laser endomicroscopy in indomethacin-induced enteropathy. Dig Dis Sci 2014; 59(7): 1398-405.
[http://dx.doi.org/10.1007/s10620-014-3076-8] [PMID: 24573719]
[48]
Nakashima M, Uematsu T, Takiguchi Y, Hayashi T. Phase I study of 2,4-diamino-6-(2,5-dichlorophenyl)-s-triazine maleate (MN-1695), a new anti-ulcer agent. Arzneimittelforschung 1984; 34(4): 492-8.
[PMID: 6540108]
[49]
Kameda Y, Ueda F. Irsogladine inhibits ionomycin-induced decrease in intercellular communication in cultured rabbit gastric epithelial cells. Jpn J Pharmacol 1995; 69(3): 223-8.
[http://dx.doi.org/10.1254/jjp.69.223] [PMID: 8699630]
[50]
Ueda F, Watanabe M, Hirata Y, Kyoi T, Kimura K. Changes in cyclic AMP content of rat gastric mucosa induced by ulcerogenic stimuli--in relation to the antiulcer activity of irsogladine maleate. Jpn J Pharmacol 1991; 55(4): 493-9.
[http://dx.doi.org/10.1254/jjp.55.493] [PMID: 1653374]
[51]
Shim KN, Kim JI, Kim N, et al. The efficacy and safety of irsogladine maleate in nonsteroidal anti-inflammatory drug or aspirin induced peptic ulcer and gastritis. Korean J Intern Med 2019; 34(5): 1008-21.
[PMID: 29847892]
[52]
Suzuki T, Matsushima M, Masui A, et al. Irsogladine maleate and rabeprazole in non-erosive reflux disease: A double-blind, placebo-controlled study. World J Gastroenterol 2015; 21(16): 5023-31.
[http://dx.doi.org/10.3748/wjg.v21.i16.5023] [PMID: 25945018]
[53]
Hayashi N, George J, Shiroeda H, et al. Irsogladine maleate for the treatment of recurrent aphthous stomatitis in hepatitis C virus patients on pegylated-interferon and ribavirin: a pilot study. J Gastroenterol Hepatol 2013; 28(6): 1015-8.
[http://dx.doi.org/10.1111/jgh.12137] [PMID: 23425065]
[54]
Fujita T, Yoshimoto T, Kajiya M, et al. Regulation of defensive function on gingival epithelial cells can prevent periodontal disease. Jpn Dent Sci Rev 2018; 54(2): 66-75.
[http://dx.doi.org/10.1016/j.jdsr.2017.11.003] [PMID: 29755617]
[55]
Feng X, Liu J. A combination of irsogladine maleate and azithromycin exhibits addictive protective effects in LPS-induced human gingival epithelial cells. Pharmazie 2017; 72(2): 91-4.
[PMID: 29441859]
[56]
Onuma W, Tomono S, Miyamoto S, et al. Irsogladine maleate, a gastric mucosal protectant, suppresses intestinal polyp development in Apc-mutant mice. Oncotarget 2016; 7(8): 8640-52.
[http://dx.doi.org/10.18632/oncotarget.7082] [PMID: 26840084]
[57]
Kojima Y, Takeuchi T, Ota K, et al. Effect of long-term proton pump inhibitor therapy and healing effect of irsogladine on nonsteroidal anti-inflammatory drug-induced small-intestinal lesions in healthy volunteers. J Clin Biochem Nutr 2015; 57(1): 60-5.
[http://dx.doi.org/10.3164/jcbn.15-32] [PMID: 26236102]
[58]
Satoh H, Amagase K, Takeuchi K. Mucosal protective agents prevent exacerbation of NSAID-induced small intestinal lesions caused by antisecretory drugs in rats. J Pharmacol Exp Ther 2014; 348(2): 227-35.
[http://dx.doi.org/10.1124/jpet.113.208991] [PMID: 24254524]
[59]
Matysiak-Budnik T, Thomas-Collignon A, Mégraud F, Heyman M. Alterations of epithelial permeability by Helicobacter and IL-1beta in vitro: protective effect of rebamipide. Dig Dis Sci 2001; 46(7): 1558-66.
[http://dx.doi.org/10.1023/A:1010664626431] [PMID: 11478510]
[60]
Joh T, Takezono Y, Oshima T, et al. The protective effect of rebamipide on paracellular permeability of rat gastric epithelial cells. Aliment Pharmacol Ther 2003; 18(Suppl. 1): 133-8.
[http://dx.doi.org/10.1046/j.1365-2036.18.s1.15.x] [PMID: 12925151]
[61]
Laharie D, Ménard S, Asencio C, et al. Effect of rebamipide on the colonic barrier in interleukin-10-deficient mice. Dig Dis Sci 2007; 52(1): 84-92.
[http://dx.doi.org/10.1007/s10620-006-9183-4] [PMID: 17186389]
[62]
Diao L, Mei Q, Xu JM, et al. Rebamipide suppresses diclofenac-induced intestinal permeability via mitochondrial protection in mice. World J Gastroenterol 2012; 18(10): 1059-66.
[http://dx.doi.org/10.3748/wjg.v18.i10.1059] [PMID: 22416180]
[63]
Lai Y, Zhong W, Yu T, et al. Rebamipide Promotes the Regeneration of Aspirin-Induced Small-Intestine Mucosal Injury through Accumulation of β-Catenin. PLoS One 2015; 10(7)e0132031
[http://dx.doi.org/10.1371/journal.pone.0132031] [PMID: 26135128]
[64]
Ito Y, Sasaki M, Funaki Y, et al. Nonsteroidal anti-inflammatory drug-induced visible and invisible small intestinal injury. J Clin Biochem Nutr 2013; 53(1): 55-9.
[http://dx.doi.org/10.3164/jcbn.12-116] [PMID: 23874071]
[65]
Mahmood A, FitzGerald AJ, Marchbank T, et al. Zinc carnosine, a health food supplement that stabilises small bowel integrity and stimulates gut repair processes. Gut 2007; 56(2): 168-75.
[http://dx.doi.org/10.1136/gut.2006.099929] [PMID: 16777920]
[66]
Zhang Q, Feng L. Protective effect of polaprezinc on acute gastric mucosal injury in rats. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2019; 44(1): 22-7.
[PMID: 30837398]
[67]
Liu Z, Xie W, Li M, et al. Oral Administration of Polaprezinc Attenuates Fluorouracil-induced Intestinal Mucositis in a Mouse Model. Basic Clin Pharmacol Toxicol 2017; 121(6): 480-6.
[http://dx.doi.org/10.1111/bcpt.12841] [PMID: 28667794]
[68]
Odawara S, Doi H, Shikata T, et al. Polaprezinc protects normal intestinal epithelium against exposure to ionizing radiation in mice. Mol Clin Oncol 2016; 5(4): 377-81.
[http://dx.doi.org/10.3892/mco.2016.983] [PMID: 27699029]
[69]
Davison G, Marchbank T, March DS, Thatcher R, Playford RJ. Zinc carnosine works with bovine colostrum in truncating heavy exercise-induced increase in gut permeability in healthy volunteers. Am J Clin Nutr 2016; 104(2): 526-36.
[http://dx.doi.org/10.3945/ajcn.116.134403] [PMID: 27357095]
[70]
Ahmad R, Sorrell MF, Batra SK, Dhawan P, Singh AB. Gut permeability and mucosal inflammation: bad, good or context dependent. Mucosal Immunol 2017; 10(2): 307-17.
[http://dx.doi.org/10.1038/mi.2016.128] [PMID: 28120842]
[71]
Fukui H. Increased Intestinal Permeability and Decreased Barrier Function: Does It Really Influence the Risk of Inflammation? Inflamm Intest Dis 2016; 1(3): 135-45.
[http://dx.doi.org/10.1159/000447252] [PMID: 29922669]
[72]
Wang N, Han Q, Wang G, et al. Resveratrol Protects Oxidative Stress-Induced Intestinal Epithelial Barrier Dysfunction by Upregulating Heme Oxygenase-1 Expression. Dig Dis Sci 2016; 61(9): 2522-34.
[http://dx.doi.org/10.1007/s10620-016-4184-4] [PMID: 27146412]
[73]
Wang N, Wang G, Hao J, et al. Curcumin ameliorates hydrogen peroxide-induced epithelial barrier disruption by upregulating heme oxygenase-1 expression in human intestinal epithelial cells. Dig Dis Sci 2012; 57(7): 1792-801.
[http://dx.doi.org/10.1007/s10620-012-2094-7] [PMID: 22392462]
[74]
Sikirić P, Petek M, Rucman R, et al. A new gastric juice peptide, BPC. An overview of the stomach-stress-organoprotection hypothesis and beneficial effects of BPC. J Physiol Paris 1993; 87(5): 313-27.
[http://dx.doi.org/10.1016/0928-4257(93)90038-U] [PMID: 8298609]
[75]
Sikiric P, Seiwerth S, Rucman R, et al. Brain-gut Axis and Pentadecapeptide BPC 157: Theoretical and Practical Implications. Curr Neuropharmacol 2016; 14(8): 857-65.
[http://dx.doi.org/10.2174/1570159X13666160502153022] [PMID: 27138887]
[76]
Sikiric P, Seiwerth S, Grabarevic Z, et al. The beneficial effect of BPC 157, a 15 amino acid peptide BPC fragment, on gastric and duodenal lesions induced by restraint stress, cysteamine and 96% ethanol in rats. A comparative study with H2 receptor antagonists, dopamine promotors and gut peptides. Life Sci 1994; 54(5): PL63-8.
[http://dx.doi.org/10.1016/0024-3205(94)00796-9] [PMID: 7904712]
[77]
Wang XY, Qu M, Duan R, et al. Cytoprotective Mechanism of the Novel Gastric Peptide BPC157 in Gastrointestinal Tract and Cultured Enteric Neurons and Glial Cells. Neurosci Bull 2019; 35(1): 167-70.
[http://dx.doi.org/10.1007/s12264-018-0269-8] [PMID: 30116973]
[78]
Sikiric P, Seiwerth S, Brcic L, et al. Revised Robert’s cytoprotection and adaptive cytoprotection and stable gastric pentadecapeptide BPC 157. Possible significance and implications for novel mediator. Curr Pharm Des 2010; 16(10): 1224-34.
[http://dx.doi.org/10.2174/138161210790945977] [PMID: 20166993]
[79]
Hsieh MJ, Liu HT, Wang CN, et al. Therapeutic potential of pro-angiogenic BPC157 is associated with VEGFR2 activation and up-regulation. J Mol Med (Berl) 2017; 95(3): 323-33.
[http://dx.doi.org/10.1007/s00109-016-1488-y] [PMID: 27847966]
[80]
Ilic S, Drmic D, Franjic S, et al. Pentadecapeptide BPC 157 and its effects on a NSAID toxicity model: diclofenac-induced gastrointestinal, liver, and encephalopathy lesions. Life Sci 2011; 88(11-12): 535-42.
[http://dx.doi.org/10.1016/j.lfs.2011.01.015] [PMID: 21295044]
[81]
Sikiric P, Hahm KB, Blagaic AB, 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 2019; •••
[PMID: 31158953]
[82]
Omatsu T, Naito Y, Handa O, et al. Involvement of reactive oxygen species in indomethacin-induced apoptosis of small intestinal epithelial cells. J Gastroenterol 2009; 44(Suppl. 19): 30-4.
[http://dx.doi.org/10.1007/s00535-008-2293-3] [PMID: 19148790]
[83]
Wan QS, Wang T, Zhang KH. Biomedical optical spectroscopy for the early diagnosis of gastrointestinal neoplasms. Tumour Biol 2017; 39(7)1010428317717984
[http://dx.doi.org/10.1177/1010428317717984] [PMID: 28671054]
[84]
Sharma N, Takeshita N, Ho KY. Raman Spectroscopy for the Endoscopic Diagnosis of Esophageal, Gastric, and Colonic Diseases. Clin Endosc 2016; 49(5): 404-7.
[http://dx.doi.org/10.5946/ce.2016.100] [PMID: 27653440]
[85]
Chernavskaia O, Heuke S, Vieth M, et al. Beyond endoscopic assessment in inflammatory bowel disease: real-time histology of disease activity by non-linear multimodal imaging. Sci Rep 2016; 6: 29239.
[http://dx.doi.org/10.1038/srep29239] [PMID: 27406831]
[86]
Takemura M, Kurimoto N, Hoshikawa M, et al. Probe-based confocal laser endomicroscopy for rapid on-site evaluation of transbronchial biopsy specimens. Thorac Cancer 2019; 10(6): 1441-7.
[http://dx.doi.org/10.1111/1759-7714.13089] [PMID: 31058452]
[87]
Park CH, Kim NH, Park JH, Park DI, Sohn CI, Jung YS. Impact of family history of colorectal cancer on age-specific prevalence of colorectal neoplasia. J Gastroenterol Hepatol 2019; 34(3): 537-43.
[PMID: 30462856]
[88]
Kollar M, Spicak J, Honsova E, Krajciova J, Vackova Z, Martinek J. Role of confocal laser endomicroscopy in patients with early esophageal neoplasia. Minerva Chir 2018; 73(4): 417-27.
[PMID: 29806759]
[89]
Kangwan N, Park JM, Hahm KB. Development of GI-safe NSAID; progression from the bark of willow tree to modern pharmacology. Curr Opin Pharmacol 2014; 19: 17-23.
[http://dx.doi.org/10.1016/j.coph.2014.06.003] [PMID: 24956584]
[90]
Lim YJ, Lee JS, Ku YS, Hahm KB. Rescue strategies against non-steroidal anti-inflammatory drug-induced gastroduodenal damage. J Gastroenterol Hepatol 2009; 24(7): 1169-78.
[http://dx.doi.org/10.1111/j.1440-1746.2009.05929.x] [PMID: 19682191]