Investigation of Plasma Amino Acid Profile in Patients with Acute Pancreatitis

Öz

Background: Acute pancreatitis (AP) is a non-bacterial acute inflammation of the pancreas that develops as a result of glandin digestion, with its enzymes leaking and activating into the parenchyma. It plays an important role in the formation of deprotein blocks as metabolic intermediates in the processes of amino acids organisms and forms an important part of metabolomic analysis. Amino acidopathies; Patients with AP show gastrointestinal dysfunction in nutrition such as acute metabolic decompensation, nausea, vomiting and gastroesophageal and abdominal pain. For this purpose, this study is to evaluate the role of the amino acid profile in the diagnosis of acute pancreatitis and that the plasma amino acid profile may play a role as a marker for its associated variation in patients with acute pancreatitis. Materials and Methods: Approximately 65 patients with acute pancreatitis were included in the study. Patients studied were included with typical abdominal pain, a 3-5-fold increase in serum amylase and lipase upper limit. In the healthy control group, 50 people were selected who had no existing disease history and pathological status.Amino acid profile measurement in plasma was examined by 8045 LC-MS / MS device. Results: In our study, the amino acids in the serum amino acid profile of patients with acute pancreatitis significantly increased the amino acids 1- methyl histidine, 2-aminoadipic acid, 2minobutric acid, 3-methyl histidine, aspartate, citrulline, glutamine methionine and valine amino acids; however, 5-hydroxyline, alanine, cysteine, tyrosine and isoleucine levels were found to be significantly decreased compared to the healthy control group (P <0.01). Keywords: Acute Pancreatitis, Free Amino acid profile, LC-MS/MS Conclusion: Physiological amino acid concentrations depend on the functions of organs and pathological conditions can alter metabolism. In recent years, amino acid profiling has been suggested in medicine as a potential marker in metabolic diseases, some scientists, acute pancratitis patients, diet proteins and amino acids have been able to regulate pancreatic function. In addition, although the proteolytic enzymes of the pancreas play a role in the formation of pancreatic inflammation, the mechanisms by which these enzymes in inactive form are activated within the pancreatic tissue are still controversial. Arginine, which is an amino acid, is metabolised to urea and ornithine with the enzyme arginase. Among the amino acids of methionine and ornithine, the combinations of polyamines, spermidine, spermin and butressins are obtained. Polyamines play an important role in cell proliferation by stimulating nucleotide and protein synthesis in cells. Levels of plasma amino acids showed the net effect of all factors affecting the flow of amino acids in the body. It is thought that the changes occurring in the presence of the infection may be transmitted by the amino acids in the plasma of these patients. As a result of our study in patients with acute pancreatitis infection, the presence of some amino acids in patients with acute pancreatitis infection is to show that these amino acids have an important role in the development of the infection and to assist physicians in deciding on this issue.

Anahtar Kelimeler

• Acute Pancreatitis
• Free Amino acid profile
• LC-MS / MS

Akut Pankreatitli Hastalarda Plazma Amino Asit Profilinin İncelenmesi

Öz

Amaç: Akut pankreatit (AP), pankreasın kendi enzimlerinin parankim içerisine sızması ve aktive olması ile glandin sindirimi sonucu gelişen, bakteriyel olmayan akut inflamasyonudur. Aminoasitler organizmalarının süreçlerinde metabolik ara maddeler olarak deprotein bloklarının oluşturulmasında önemli rol oynamakta ve metabolomik analizlerin önemli bir parçasını oluşturmaktadır. Amino asidopatiler; AP’li hastalar, akut metabolik dekompansasyonun, bulantı, kusma ve gastroözofageal ve karın ağrısı gibi beslenmede gastrointestinal fonksiyon bozukluğu gösterir. Bu amaçla, plazma aminoasit profilinin akut pankreatitli hastalarda bağlantılı varyasyonu için bir marker olarak rolü alabileceğine dair bu çalışma yapmayı ve akut pankreatit tanısında aminoasit profilinin rolünü değerlendirmektir. Materyal ve Metod : Çalışmaya 65 akut pankreatatli hasta, Çalışılan hastalar da tipik karın ağrısı, serum amilaz ve lipazı üst sınırın 3-5 kat artışı ile konuldu. Sağlıklı kontrol grubunda 50 kişi mevcut hastalık öyküsü ve patolojik durumu olmayanlar seçildi. Plazmada aminoasit profili ölçümü 8045 LC-MS/MS cihazında çalışıldı. Bulgular: Yaptığımız çalışmada akut pankreatitli hastaların serum amino asit profilineki amino asitlerin 1- metil histidine, 2-aminoadipik asit, 2-minobutrik asit, 3-metil histidine, aspartat, sitrulin, glutamin metiyonin ve valine amino asitlerinin anlamlı olarak arttığı; ancak 5-hidroksilizin, alanin, sistine, tirozin ve izolösin seviyeleri nin sağlıklı kontrol grubu ile karşılaştırıldığında anlamlı olarak düştüğü saptandı (p<0.01). Sonuç: Fizyolojik aminoasit konsantrasyonları organların işlevlerine bağlıdır ve patolojik koşullar metabolizmasında değişiklik yapabilir. Son yıllarda, aminoasit profillemesi tıp biliminde metabolik hastalıklar, bazı bilim adamları, akut pankratit hastalarda bir potansiyel belirteç olarak kullanıldığı, diyet proteinleri ve aminoasitler pankreas fonksiyonunu düzenleyebildiğini ileri sürmüşlerdir. Ayrıca pankreatik enflamasyonun oluşmasında pankreasın proteolitik enzimleri rol oynadığı bilinse de inaktif formdaki bu enzimlerin pankreas dokusu içinde hangi mekanizmalarla aktive oldukları halen tartışma konusudur. Aminoasit olan arginin arginaz enzimiyle üre ve ornitine metabolize olmaktadır. Metiyonin ve ornitin amino asitlerinden ise poliaminler olan spermidin, spermin ve pütressinler bileşimleri elde edilir. Poliaminler hücrelerde nükleotid ve protein sentezini uyararak hücre proliferasyonunda önemli görevlerde yer alır. Plazma aminoasitlerinin seviyeleri vücuttaki aminoasitlerin akışına tesir eden tüm faktörlerin net tesirini gösterdi. Enfeksiyonun varlığında oluşan değişikliklerin bu hastaların plazmalarındaki aminoasitler tarafından iletiliyor olabileceği düşünülmektedir. Akut pankreatit enfeksiyonu hastalarda yapacak olduğumuz çalışma sonucunda bazı aminoasitlerin akut pankreatit enfeksiyonlu hastalarda bulunması, bu aminoasitlerin enfeksiyonun gelişimi yönünde önemli bir role sahip olduğunu göstermek ve hekimlere bu konu hakkında karar verirken yardımcı olabilmektir.

Anahtar Kelimeler

• Akut Pankreatit
• Serbest Aminoasit profili
• LC-MS/MS

Kaynakça

1. 1. Sternby H, Mahle M, Linder N, Erichson K L, Mean muscle attenuation correlates with severe acute pancreatitis unlike visceral adipose tissue and subcutaneous adipose tissue. United European Gastroenterol J. 2019; 7(10):1312–1320. https:// doi: 10.1177/2050640619882520
2. 2. Zheng Z, Ding Y, Xu Qu Y, Cao F, Li F.A narrative review of acute pancreatitis and its diagnosis, pathogenetic mechanism, andmanagement. Ann Transl Med. 2021; 9(1): 69. https:// doi:// 10.21037/atm-20-4802.
3. 3. Meher S, Subhadarshan M T, Sasmal P K, t Rathet S et al. Role of Biomarkers in Diagnosis and Prognostic Evaluation of Acute Pancreatitis. Rakesh Sharma, Bikram Rout, Manoj Kumar Sahu. J Biomark. 2015; 519534. https:// doi: //10.1155/2015/519534
4. 4. Knerr I, Weinhold N, Vockley J, K. Gibson M. Advances and challenges in the treatment of branched-chain amino/keto acid metabolicdefects. J Inherit Metab Dis. Author manuscript; available in PMC 2014 Aug 18. Published in final edited form as: J Inherit Metab Dis. 2012; 35(1): 29–40. https:// doi: //10.1007/s10545-010-9269-1.
5. 5. Beth K. Potter, Chakraborty Ph, Jonathan B. Kronick, n Wilson K, Doug Coyle, Annette Feigenbaum, Michael T. Geraghty, Maria D. Karaceper, Julian Little, Aizeddin Mhanni, John J. Mitchell, Komudi Siriwardena, Brenda J. Wilson, Ania Syrowatka, ; on behalf of the Canadian Inherited Metabolic Diseases Research Network. Genet Med. 2013 https:// doi: 10.1038/gim.2012.153.
6. 6. Shah P A, Mourad M M, Bramhall S R. Acute pancreatitis: current perspectives on diagnosis and management. J Inflamm Res. 2018; 11: 77–85. Published online 2018 Mar 9. https:// doi: 10.2147/JIR.S135751.
7. 7. Mayerle J, Sendler M, r Hegyi E, Beyer G etal.. Genetics and pathophysiology of pancreatitis. Gastroenterology. Author manuscript; available in PMC 2020,Published in final edited form as: Gastroenterology. 2019; 156(7): 1951–1968.e1. Published //online 2019 Jan 18. . https://doi: 10.1053/j.gastro.2018.11.081
8. 8. Noel P, Patel K, Durgampudi C, Trivedi R N, C de Oliveira. Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections. Et al. Gut. Gut. 2016; 65(1): 100–111. Published online 2014; 10. https:// doi: 10.1136/gutjnl-2014-308043.

9. 9. Gunn IR, Faye S, Clavron MG. Prospective evaluation of urinary amylase test strip. Lancet 1986; 11: 51-62. Serum amylase and lipase and urinary trypsinogen and amylase for diagnosis of acute pancreatitisCochrane Database Syst Rev. 2017 Apr; 2017(4): CD012010; https:// doi: 10.1002/14651858.CD012010.pub2
10. 10. Wong ECC, Burch AW, Rosenblum JL, Ladenson LH, Score MG. The clinical chemistry laboratory and pancreatitis. ClinChem 1993; 39: 234-243.
11. 11. Zheng Z, Ding YX, Xu Qu Y, Cao F, L Fei. A narrative review of acute pancreatitis and its diagnosis, pathogenetic mechanism, and management.Ann Transl Med. 2021; 9(1): 69. https:// doi: 10.21037/atm-20-4802.
12. 12. Kleinhans H, Mann O, Schurr P G, T J Kaifi et al.,Oxygen radical formation does not have an impact in the treatment of severe acute experimental pancreatitis using free cellular hemoglobin. World J Gastroenterol. 2006;14; 12(18): 2https:// doi: 10.3748/wjg.v12.i18.2914PMCID.
13. 13. Salvador Pérez, Javier Pereda, Luis Sabater, Juan Sastre. Redox signaling in acute pancreatitis. Redox Biol. 2015https:// doi: 10.1016/j.redox.2015.01.014.
14. 14. Susanta Meher, Tushar Subhadarshan Mishra, Prakash Kumar Sasmal, Satyajit Rath, Role of Biomarkers in Diagnosis and Prognostic Evaluation of Acute Pancreatitis. Rakesh Sharma, Bikram Rout, Manoj Kumar Sahu J Biomark. 2015; https:// doi: 10.1155/2015/519534.
15. 15. Dóra Mosztbacher, Zsanett Jancsó, Miklós Sahin-Tóth. Loss of chymotrypsin-like protease (CTRL) alters intrapancreatic protease activation but not pancreatitis severity in mice. Sci Rep. 2020; 10: 11731. Published online 2020; https:// doi: 10.1038/s41598-020-68616-9.
16. 16. Testoni PA. Acute recurrent pancreatitis: Etiopathogenesis, diagnosis and treatment. World J Gastroenterol. 2014; 20(45): 16891–16901https:// doi: 10.3748/wjg.v20.i45.16891.
17. 17. Francesca Urbano, Marco Bugliani, Agnese Filippello, Alessandra Scamporrino. Atorvastatin but Not Pravastatin Impairs Mitochondrial Function in Human Pancreatic Islets and Rat β-Cells. Direct Effect of Oxidative Stress. Sci Rep. 2017; https:// doi: 10.1038/s41598-017-11070-x. Sci Rep. 2020; 10: 22034.
18. 18. Sadighara M, Joktaji JP, Hajhashemi V, Minaiyan M. .Protective effects of coenzyme Q10 and L-carnitine against statin-induced pancreatic mitochondrialtoxicity in rats. Res Pharm Sci. 2017; 12(6): 434–443. https:// doi: 10.4103/1735-5362.217424.
19. 19. Zhang X, Jin T, Shi N, Yao L, Yang X, Han C, et al. Mechanisms of Pancreatic Injury Induced by Basic Amino Acids Differ Between l-Arginine, l-Ornithine, and l-Histidine Front Front Physiol. 2018;https:// doi: 10.3389/fphys.2018.01922. PMCID: PMC6341295.
20. 20. H. Rinderknecht, I. G. Renner, C. Carmack. Trypsinogen variants in pancreatic juice of healthy volunteers, chronic alcoholics, and patients with pancreatitis and cancer of the pancreas. Gut. 1979; 20(10): 886–891. https:// doi: 10.1136/gut.20.10.886.
21. 21. Pang Y, Kartsonaki C, Turnbull I, Guo Y. Metabolic and lifestyle risk factors for acute pancreatitis in Chinese adults: A prospective cohort study of 0.5 million people. PLoS Med. 2018; 15(8): https:// doi: 10.1371/journal.pmed.1002618.
22. 22. Vadlakonda L, Indracanti M, Kalangi S K, Gayatri M,et al. The Role of Pi, Glutamine and the Essential Amino Acids in Modulating the Metabolism in Diabetes and Cancer. J Diabetes Metab Disord. 2020; 19(2): 1731–1775. https:// doi: 10.1007/s40200-020-00566-5.
23. 23. Garib R, Garla P, Torrinhas RS., Moretti Ana IS, et al. Effect of Previous High Glutamine Infusion on Inflammatory Mediators and Mortality in an Acute Pancreatitis Model. Mediators Inflamm. 2016; online 2016. https:// doi: 10.1155/2016/4261419.
24. 24. Lugea A, Waldron R T, Olga AM, Shalbueva N, Deng N, S Hsin-Yuan, et al. Human Pancreatic Acinar Cells: Proteomic Characterization, Physiologic Responses, and Organellar Disorder in ex Vivo Pancreatitis. Am J Pathol. Am J Pathol. 2017; 187(12): 2726–2743. https:// doi: 10.1016/j.ajpath.2017.08.01.
25. 25. Gukovskaya AS., Gorelick FS., Groblewski GE., Mareninova OA., et al. Recent Insights Into the Pathogenic Mechanism of Pancreatitis: Role of Acinar Cell Organelle Disorders. Pancreas. 2019; 48(4): 459–470. https:// doi: 10.1097/MPA.0000000000001298.
26. 26. Adrych K, Smoczynski M, Stojek M, Sledzinski T, Slominska E, Goyke E, et al. Decreased serum essential and aromatic acid in patients with chronic pancreatitis. World J Gastroenterol. 2010;16(35):4422–4. 21; 16(35): 4422–4427. https:// doi: 10.3748/wjg.v16.i35.4422.
27. 27. Zhang X, Jin T, Shi N, Yao L et al. Mechanisms of Pancreatic Injury Induced by Basic Amino Acids Differ Between L-Arginine, L-Ornithine, and L-Histidine Front Physiol. 2018; 9: 1922. Published online 2019; https:// doi: 10.3389/fphys.2018.01922.
28. 28. Ramírez-Zamora S, L M Méndez-Rodríguez, Olguín-Martínez M , Sánchez-Sevilla Lourdes, Increased Erythrocytes By-Products of Arginine Catabolism Are Associated with Type 2 Diabetes Mellitus. PLoS One. 2013; 8(6): e66823. Published online 2013; https:// doi: 10.1371/journal.pone.0066823.
29. 29. Yang L, Jia Q S, He SS, Hu GY, et al. L Cysteine Administration Attenuates Pancreatic Fibrosis Induced by TNBS in Rats by Inhibiting the Activation of Pancreatic Stellate Cell PLoS One. 2012; 7(2): e31807. Published online 2012 16. https:// doi: 10.1371/journal.pone.0031807.
30. 30. Hobbs P M , Johnson G W , and Graham Y D. Management of pain in chronic pancreatitis with emphasis on exogenous pancreatic enzymes. World J Gastrointest Pharmacol Ther. 2016;7(3):370–386. https:// doi: 10.4292/wjgpt.v7.i3.370.