Bağırsaklar, besinlerin sindirimi ve emilimi ile birlikte canlıları çevresel tehditlere karşı koruyan bir immünolojik organ özelliğine sahiptir. Enterokolitis, ince bağırsakların yangısı olan enteritis ve kolonun yangısı olan kolitisi içeren sindirim kanalının yangısı olarak tanımlanmaktadır. Bakteriyel, viral, protozoal, fungal, paraziter etkenlere ve diğer nedenlere bağlı oluşan bu durum önemli derecede su, besin ve mineral kayıpları ile seyredebilmektedir. Enterokolitislerin seyri sırasında bağırsaklarda gelişen villus hasarı, epitel yüzeyinde azalma, sindirim ve emilim kapasitesinin önemli derecede azalmasına neden olmakta ve bu hasarın şiddetinin belirlenmesi gerektiğinde sıklıkla geleneksel invaziv metotlara ihtiyaç duyulmaktadır. Bu pratik olmayan metotlar, günümüzde yerini hastalığın şiddetini, varlığını ve seyrini gösterebilen kanda bulunan proteinlerin ölçülmesi olarak tanımlanabilen biyobelirteçlere bırakmaya başlamış, son yıllarda hem beşerî hem veteriner hekimlikte çalışma konusu olmuştur. Yapılan çalışmalar, biyobelirteçlerin kan ve idrardaki salınım miktarının, çeşitli bağırsak hastalıklarının seyri esnasında değişiklik gösterdiğini ortaya koymaktadır. Bununla birlikte bazı biyobelirteçlerin, bağırsaklar üzerinde koruyucu etkilerinin de olduğu bildirilmektedir. Bu derlemede, bağırsak ile ilgili biyobelirteçler arasından seçilen yağ asidi bağlayıcı proteinler, trefoil faktör 3, intestinal alkalin fosfataz, klaudinler, bağırsak düz kas aktini, platelet aktive edici faktör, leptin ve interlökin 8 ve bu biyobelirteçlerin; enterokolitislerde değerlendirilmesi, teşhisteki kullanımları, veteriner hekimlik için önemi hakkında yeni ve güncel bilgiler sunulması amaçlanmıştır.
Anahtar Kelimeler: Enterokolitis; teşhis; bağırsak biyobelirteç
As commonly known, the intestines are immunological organ that protects living beings against environmental threats as well as with the properties of digestion and absorption of nutrients. Enterocolitis is defined as the inflammation of the digestive tract, including enteritis that is the inflammation of the small intestines and also colitis that is the inflammation of the colon. This condition, which occurs due to bacterial, viral, protozoal, fungal, parasitic factors and other causes, may progress with significant water, nutrient and mineral losses. During the progress of enterocolitis, the villus damage that develops in the intestines and the reduction in the epithelial surface cause a prominent decrease in the digestion and absorption capacity, and to determine the severity of the damage conventional invasive methods are often required. These impractical methods have begun to be replaced by biomarkers which have been the subject of both human and veterinary medicine in recent years that can be defined as the measurement of proteins in blood that can indicate the severity, presence and progress of the disease. Studies show that the amount of released biomarkers into blood and urine varies during the course of diverse bowel diseases. However, some biomarkers are reported to have protective effects on the intestines. In this review, it was aimed to present new and updated information about selected intestinal-related biomarkers such as fatty acid binding proteins, trefoil factor 3, intestinal alkaline phosphatase, claudins, intestinal smooth muscle actin, platelet activating factor, leptin and interleukin 8 and the evaluation of these biomarkers in enterocolitis, their use in diagnosis, and their importance for veterinary medicine.
Keywords: Enterocolitis; diagnosis; intestinal biomarker
- Turgut K, Ok M. Kedi ve Köpek Gastroenterolojisi. 1. Baskı. Konya: Bahçıvanlar Basımevi; 2001. p.283-421.
- Lu Z, Ding L, Lu Q, Chen YH. Claudins in intestines: Distribution and functional significance in health and diseases. Tissue Barriers. 2013;1(3):e24978. [Crossref] [PubMed] [PMC]
- Furuhashi M, Hotamisligil GS. Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets. Nat Rev Drug Discov. 2008;7(6):489-503. [Crossref] [PubMed] [PMC]
- Ok M, Yildiz R, Hatipoglu F, Baspinar N, Ider M, Üney K, et al. Use of intestine-related biomarkers for detecting intestinal epithelial damage in neonatal calves with diarrhea. Am J Vet Res. 2020;81(2):139-46. [Crossref] [PubMed]
- Yildiz R, Ok M, Ider M, Aydogdu U, Naseri A, Parlak K, et al. Evaluation of intestinal damage biomarkers in calves with atresia coli. J Vet Res. 2018;62(3):379-84. [Crossref] [PubMed] [PMC]
- Yildiz R, Ok M, Ider M, Akar A, Naseri A, Koral E. The changes in biomarkers for necrotising enterocolitis in premature calves with respiratory distress syndrome. Vet Med (Praha). 2019;64(10):440-7. [Crossref]
- Ettinger SJ, Edward CF, Cote E. Textbook of Veterinary Internal Medicine. In: Hall JE, Day MJ. Small Intestine Diseases. 8th ed. Missouri: Elsevier; 2018. p.3643-820.
- Ng EW, Poon TC, Lam HS, Cheung HM, Ma TP, Chan KY, et al. Gut-associated biomarkers L-FABP, I-FABP, and TFF3 and LIT score for diagnosis of surgical necrotizing enterocolitis in preterm infants. Ann Surg. 2013;258(6):1111-8. [Crossref] [PubMed]
- Arisanti D, Wibowo S, Soemarno S. Calprotectin and intestinal fatty acid binding protein (I-FABP) level in preterm neonates with necrotizing enterocolitis. Res J Biol Sci. 2019;6(1):1-10. [Crossref]
- Thuijls G, Derikx JP, van Wijck K, Zimmermann LJ, Degraeuwe PL, Mulder TL, et al. Non-invasive markers for early diagnosis and determination of the severity of necrotizing enterocolitis. Ann Surg. 2010;251(6):1174-80. [Crossref] [PubMed]
- Molnár K, Vannay A, Szebeni B, Bánki NF, Sziksz E, Cseh A, et al. Intestinal alkaline phosphatase in the colonic mucosa of children with inflammatory bowel disease. World J Gastroenterol. 2012;18(25):3254-9. [PubMed] [PMC]
- Saltiel AR, Kahn CR. Insulin signalling and the regulation of glucose and lipid metabolism. Nature. 2001;414(6865):799-806. [Crossref] [PubMed]
- Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444(7121):860-7. [Crossref] [PubMed]
- Ockner RK, Manning JA, Poppenhausen RB, Ho WK. A binding protein for fatty acids in cytosol of intestinal mucosa, liver, myocardium, and other tissues. Science. 1972;177(4043):56-8. [Crossref] [PubMed]
- Veerkamp JH, van Moerkerk HT. Fatty acid-binding protein and its relation to fatty acid oxidation. In: Glatz JFC, van der Vusse GJ, eds. Cellular Fatty Acid-Binding Proteins II. 1st ed. Boston: Springer; 1993. p.101-6. [Crossref] [PubMed]
- Tuğlu B, Uysal S. Yağ asidi bağlayıcı proteinler [Fatty acid binding proteins]. Turk J Biochem. 2011;9(1):31-8. [Link]
- Gollin G, Marks C, Marks WH. Intestinal fatty acid binding protein in serum and urine reflects early ischemic injury to the small bowel. Surgery. 1993;113(5):545-51. [PubMed]
- Pelsers MM, Namiot Z, Kisielewski W, Namiot A, Januszkiewicz M, Hermens WT, et al. Intestinal-type and liver-type fatty acid-binding protein in the intestine. Tissue distribution and clinical utility. Clin Biochem. 2003;36(7):529-35. [Crossref] [PubMed]
- Thuijls G, Derikx JP, de Haan JJ, Grootjans J, de Bruïne A, Masclee AA, et al. Urine-based detection of intestinal tight junction loss. J Clin Gastroenterol. 2010;44(1):e14-9. [Crossref] [PubMed]
- Thim L. Trefoil peptides: a new family of gastrointestinal molecules. Digestion. 1994;55(6):353-60. [Crossref] [PubMed]
- Emami S, Rodrigues S, Rodrigue CM, Le Floch N, Rivat C, Attoub S, et al. Trefoil factor family (TFF) peptides and cancer progression. Peptides. 2004;25(5):885-98. [Crossref] [PubMed]
- Tran CP, Cook GA, Yeomans ND, Thim L, Giraud AS. Trefoil peptide TFF2 (spasmolytic polypeptide) potently accelerates healing and reduces inflammation in a rat model of colitis. Gut. 1999;44(5):636-42. [Crossref] [PubMed] [PMC]
- Lin J, Holzman IR, Jiang P, Babyatsky MW. Expression of intestinal trefoil factor in developing rat intestine. Biol Neonate. 1999;76(2):92-7. [Crossref] [PubMed]
- Furuta GT, Turner JR, Taylor CT, Hershberg RM, Comerford K, Narravula S, et al. Hypoxia-inducible factor 1-dependent induction of intestinal trefoil factor protects barrier function during hypoxia. J Exp Med. 2001;193(9):1027-34. [Crossref] [PubMed] [PMC]
- Yang Y, Wandler AM, Postlethwait JH, Guillemin K. Dynamic evolution of the LPS-detoxifying enzyme intestinal alkaline phosphatase in zebrafish and other vertebrates. Front Immunol. 2012;3:314. [Crossref] [PubMed] [PMC]
- Malo MS, Moaven O, Muhammad N, Biswas B, Alam SN, Economopoulos KP, et al. Intestinal alkaline phosphatase promotes gut bacterial growth by reducing the concentration of luminal nucleotide triphosphates. Am J Physiol Gastrointest Liver Physiol. 2014;306(10):G826-38. [Crossref] [PubMed] [PMC]
- Martínez-Moya P, Ortega-González M, González R, Anzola A, Ocón B, Hernández-Chirlaque C, et al. Exogenous alkaline phosphatase treatment complements endogenous enzyme protection in colonic inflammation and reduces bacterial translocation in rats. Pharmacol Res. 2012;66(2):144-53. [Crossref] [PubMed]
- Lallès JP. Intestinal alkaline phosphatase: multiple biological roles in maintenance of intestinal homeostasis and modulation by diet. Nutr Rev. 2010;68(6):323-32. [Crossref] [PubMed]
- Fawley J, Gourlay DM. Intestinal alkaline phosphatase: a summary of its role in clinical disease. J Surg Res. 2016;202(1):225-34. [Crossref] [PubMed] [PMC]
- Janssens S, Beyaert R. Role of Toll-like receptors in pathogen recognition. Clin Microbiol Rev. 2003;16(4):637-46. [Crossref] [PubMed] [PMC]
- Estaki M, DeCoffe D, Gibson DL. Interplay between intestinal alkaline phosphatase, diet, gut microbes and immunity. World J Gastroenterol. 2014;20(42):15650-6. [Crossref] [PubMed] [PMC]
- Rietschel ET, Kirikae T, Schade FU, Mamat U, Schmidt G, Loppnow H, et al. Bacterial endotoxin: molecular relationships of structure to activity and function. FASEB J. 1994;8(2):217-25. [Crossref] [PubMed]
- Bentala H, Verweij WR, Huizinga-Van der Vlag A, van Loenen-Weemaes AM, Meijer DK, Poelstra K. Removal of phosphate from lipid A as a strategy to detoxify lipopolysaccharide. Shock. 2002;18(6):561-6. [Crossref] [PubMed]
- Tuin A, Poelstra K, de Jager-Krikken A, Bok L, Raaben W, Velders MP, et al. Role of alkaline phosphatase in colitis in man and rats. Gut. 2009;58(3):379-87. [Crossref] [PubMed]
- Riggle KM, Rentea RM, Welak SR, Pritchard KA Jr, Oldham KT, Gourlay DM. Intestinal alkaline phosphatase prevents the systemic inflammatory response associated with necrotizing enterocolitis. J Surg Res. 2013;180(1):21-6. [Crossref] [PubMed] [PMC]
- Koyama I, Matsunaga T, Harada T, Hokari S, Komoda T. Alkaline phosphatases reduce toxicity of lipopolysaccharides in vivo and in vitro through dephosphorylation. Clin Biochem. 2002;35(6):455-61. [Crossref] [PubMed]
- Goldberg RF, Austen WG Jr, Zhang X, Munene G, Mostafa G, Biswas S, et al. Intestinal alkaline phosphatase is a gut mucosal defense factor maintained by enteral nutrition. Proc Natl Acad Sci U S A. 2008;105(9):3551-6. [Crossref] [PubMed] [PMC]
- Laukoetter MG, Bruewer M, Nusrat A. Regulation of the intestinal epithelial barrier by the apical junctional complex. Curr Opin Gastroenterol. 2006;22(2):85-9. [Crossref] [PubMed]
- Turksen K, Troy TC. Barriers built on claudins. J Cell Sci. 2004;117(Pt 12):2435-47. Erratum in: J Cell Sci. 2004;117(Pt 18):4341. [Crossref] [PubMed]
- Van Itallie CM, Anderson JM. Claudins and epithelial paracellular transport. Annu Rev Physiol. 2006;68:403-29. [Crossref] [PubMed]
- Lal-Nag M, Morin PJ. The claudins. Genome Biol. 2009;10(8):235. [Crossref] [PubMed] [PMC]
- Lameris AL, Huybers S, Kaukinen K, Mäkelä TH, Bindels RJ, Hoenderop JG, et al. Expression profiling of claudins in the human gastrointestinal tract in health and during inflammatory bowel disease. Scand J Gastroenterol. 2013;48(1):58-69. [Crossref] [PubMed]
- Patel RM, Myers LS, Kurundkar AR, Maheshwari A, Nusrat A, Lin PW. Probiotic bacteria induce maturation of intestinal claudin 3 expression and barrier function. Am J Pathol. 2012;180(2):626-35. Erratum in: Am J Pathol. 2012;180(3):1324. [Crossref] [PubMed] [PMC]
- Karaki S, Kaji I, Otomo Y, Tazoe H, Kuwahara A. The tight junction component protein, claudin-4, is expressed by enteric neurons in the rat distal colon. Neurosci Lett. 2007;428(2-3):88-92. [Crossref] [PubMed]
- Ohta H, Yamaguchi T, Rajapakshage BK, Murakami M, Sasaki N, Nakamura K, et al. Expression and subcellular localization of apical junction proteins in canine duodenal and colonic mucosa. Am J Vet Res. 2011;72(8):1046-51. [Crossref] [PubMed]
- Ding L, Lu Z, Foreman O, Tatum R, Lu Q, Renegar R, et al. Inflammation and disruption of the mucosal architecture in claudin-7-deficient mice. Gastroenterology. 2012;142(2):305-15. [Crossref] [PubMed] [PMC]
- Tamura A, Kitano Y, Hata M, Katsuno T, Moriwaki K, Sasaki H, et al. Megaintestine in claudin-15-deficient mice. Gastroenterology. 2008;134(2):523-34. [Crossref] [PubMed]
- Tamura A, Hayashi H, Imasato M, Yamazaki Y, Hagiwara A, Wada M, et al. Loss of claudin-15, but not claudin-2, causes Na+ deficiency and glucose malabsorption in mouse small intestine. Gastroenterology. 2011;140(3):913-23. [Crossref] [PubMed]
- Ivanov AI, Nusrat A, Parkos CA. The epithelium in inflammatory bowel disease: potential role of endocytosis of junctional proteins in barrier disruption. Novartis Found Symp. 2004;263:115-24; discussion 124-32, 211-8. [Crossref] [PubMed]
- Zeissig S, Bürgel N, Günzel D, Richter J, Mankertz J, Wahnschaffe U, et al. Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease. Gut. 2007;56(1):61-72. [Crossref] [PubMed] [PMC]
- Mennigen R, Nolte K, Rijcken E, Utech M, Loeffler B, Senninger N, et al. Probiotic mixture VSL#3 protects the epithelial barrier by maintaining tight junction protein expression and preventing apoptosis in a murine model of colitis. Am J Physiol Gastrointest Liver Physiol. 2009;296(5):G1140-9. [Crossref] [PubMed]
- Szakál DN, Gyorffy H, Arató A, Cseh A, Molnár K, Papp M, et al. Mucosal expression of claudins 2, 3 and 4 in proximal and distal part of duodenum in children with coeliac disease. Virchows Arch. 2010;456(3):245-50. [Crossref] [PubMed]
- Lattanzi G, Cenni V, Marmiroli S, Capanni C, Mattioli E, Merlini L, et al. Association of emerin with nuclear and cytoplasmic actin is regulated in differentiating myoblasts. Biochem Biophys Res Commun. 2003;303(3):764-70. [Crossref] [PubMed]
- Evennett N, Cerigioni E, Hall NJ, Pierro A, Eaton S. Smooth muscle actin as a novel serologic marker of severe intestinal damage in rat intestinal ischemia-reperfusion and human necrotising enterocolitis. J Surg Res. 2014;191(2):323-30. [Crossref] [PubMed]
- Englberger W, Bitter-Suermann D, Hadding U. Influence of lysophospholipids and PAF on the oxidative burst of PMNL. Int J Immunopharmacol. 1987;9(3):275-82. [Crossref] [PubMed]
- MacKendrick W, Hill N, Hsueh W, Caplan M. Increase in plasma platelet-activating factor levels in enterally fed preterm infants. Biol Neonate. 1993;64(2-3):89-95. [Crossref] [PubMed]
- Caplan MS, Sun XM, Hseuh W, Hageman JR. Role of platelet activating factor and tumor necrosis factor-alpha in neonatal necrotizing enterocolitis. J Pediatr. 1990;116(6):960-4. [Crossref] [PubMed]
- Zimmerman BJ, Granger DN. Reperfusion injury. Surg Clin North Am. 1992;72(1):65-83. [Crossref] [PubMed]
- Caplan MS, Adler L, Kelly A, Hsueh W. Hypoxia increases stimulus-induced PAF production and release from human umbilical vein endothelial cells. Biochim Biophys Acta. 1992;1128(2-3):205-10. [Crossref] [PubMed]
- Martin CR, Walker WA. Intestinal immune defences and the inflammatory response in necrotising enterocolitis. Semin Fetal Neonatal Med. 2006;11(5):369-77. [Crossref] [PubMed]
- Yıldız R, Beslek M, Beydilli Y, Özçelik MM, Biçici Ö. Evaluation of platelet activating factor in neonatal calves with sepsis. Vet Hekim Der Derg. 2018;89(2):66-73. [Link]
- Baggiolini M, Walz A, Kunkel SL. Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest. 1989;84(4):1045-9. [Crossref] [PubMed] [PMC]
- Neu J. Neonatal necrotizing enterocolitis: an update. Acta Paediatr Suppl. 2005;94(449):100-5. [Crossref] [PubMed]
- Mukaida N, Shiroo M, Matsushima K. Genomic structure of the human monocyte-derived neutrophil chemotactic factor IL-8. J Immunol. 1989;143(4):1366-71. [PubMed]
- Daig R, Andus T, Aschenbrenner E, Falk W, Schölmerich J, Gross V. Increased interleukin 8 expression in the colon mucosa of patients with inflammatory bowel disease. Gut. 1996;38(2):216-22. [Crossref] [PubMed] [PMC]
- Benkoe TM, Mechtler TP, Weninger M, Pones M, Rebhandl W, Kasper DC. Serum levels of interleukin-8 and gut-associated biomarkers in diagnosing necrotizing enterocolitis in preterm infants. J Pediatr Surg. 2014;49(10):1446-51. [Crossref] [PubMed]
- Özkan KU, İnanç F, Kılınç M, Boran Ç. Leptin tedavisi yeni doğan rat incebarsağında hipoksi/reoksijenasyon hasarına karşı koruyucu mudur? [Effect of leptin treatment on small intestinal damage induced by hypoxia reoxygenation in newborn rats]. Fırat Tıp Dergisi. 2005;10(1):5-9. [Link]
- Gaigé S, Abysique A, Bouvier M. Effects of leptin on cat intestinal motility. J Physiol. 2003;546(Pt 1):267-77. [Crossref] [PubMed] [PMC]
- Saleri R, Giustina A, Tamanini C, Valle D, Burattin A, Wehrenberg WB, et al. Leptin stimulates growth hormone secretion via a direct pituitary effect combined with a decreased somatostatin tone in a median eminence-pituitary perifusion study. Neuroendocrinology. 2004;79(4):221-8. [Crossref] [PubMed]
- Liu DR, Xu XJ, Yao SK. Increased intestinal mucosal leptin levels in patients with diarrhea-predominant irritable bowel syndrome. World J Gastroenterol. 2018;24(1):46-57. [Crossref] [PubMed] [PMC]
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