Investigation of Cytokines, Biochemical Parameters and Oxidative Stress Levels in Serum of Patients with Acute Pancreatitis

Year 2024, Volume: 34 Issue: 2, 158 - 165, 30.04.2024

Nihayet Bayraktar , Oruç Aslan , Ahmet Uyanıkoğlu , Ali Öztürk , Mehmet Bayraktar , Hamza Erdoğdu

https://doi.org/10.54005/geneltip.1264527

Abstract

Objective: This study aimed to find new serum biochemistry parameters, especially for the early identification of severe AP. In the study serum cytokine levels (TNF-A, IL-1, IL-6, IL-10, IL-21), biochemical parameters (Aquaporin-1, Hepcidine, Iron, Zinc, Copper, Nitric Oxide, C-Reactive protein), and oxidative stress parameters analysis were performed.
Method: A total of 46 patients with AP and 46 healthy controls were included in this study. Serum cytokine levels, biochemical, and oxidative stress parameters by the ELISA method, and CRP by the immunoturbidimetric method were measured.
Results: When patients with AP and control groups were compared, all studied parameters were found to be statistically significant (p<0.05). However, IL-1 was found to be insignificant (p>0.05). Therefore, the Mann-Whitney U test, which is a non-parametric test, was found suitable to determine whether there was a significant difference between the patient and control groups.
Conclusions: Investigating the role of cytokines, oxidative stress and other biochemical parameters in the pathogenesis and course of the disease may contribute to a better understanding of the disease process and its therapeutic value. It showed a significant increase in oxidative stress parameters and biochemical parameters such as aquaporin-1, hepcidin, lipase, and amylase, which may help in the diagnosis of AP.

Keywords

Acute pancreatitis, cytokine, oxidative stress, some other biochemical parameters

Project Number

19092

Akut Pankreatitli Hastaların Serumlarında Sitokinler, Biyokimyasal Parametreler ve Oksidatif Stres Düzeylerinin Araştırılması

Abstract

Amaç: Bu çalışma, özellikle şiddetli AP'nin erken teşhisi için yeni serum biyokimya parametreleri bulmayı amaçladı. Çalışmada serum sitokin seviyeleri (TNF-A, IL-1, IL-6, IL-10, IL-21), biyokimyasal parametreler (Aquaporin-1, Hepsidin, Demir, Çinko, Bakır, Nitrik Oksit, C-Reaktif protein) ve oksidatif stres parametreleri analizi yapıldı.
Yöntem: Bu çalışmaya AP'li toplam 46 hasta ve 46 sağlıklı kontrol dahil edildi. ELISA yöntemi ile serum sitokin düzeyleri, biyokimyasal ve oksidatif stres parametreleri, immünotürbidimetrik yöntemle de CRP ölçüldü.
Bulgular: AP'li hastalar ve kontrol grubu karşılaştırıldığında çalışılan tüm parametreler istatistiksel olarak anlamlı bulundu (p<0.05). Ancak IL-1'in önemsiz olduğu bulundu (p>0.05). Bu nedenle hasta ve kontrol grupları arasında anlamlı fark olup olmadığını belirlemek için parametrik olmayan bir test olan Mann-Whitney U testi uygun bulunmuştur.
Sonuç: Sitokinlerin, oksidatif stresin ve diğer biyokimyasal parametrelerin hastalığın patogenezindeki ve seyrindeki rolünün araştırılması, hastalık sürecinin ve tedavi edici değerinin daha iyi anlaşılmasına katkı sağlayabilir. AP tanısında yardımcı olabilecek aquaporin-1, hepsidin, lipaz ve amilaz gibi oksidatif stres parametrelerinde ve biyokimyasal parametrelerde önemli bir artış gösterdi.

Keywords

Akut pankreatit, sitokin, oksidatif stres, diğer bazı biyokimyasal parametreler

Supporting Institution

HARRAN ÜNİVERSİTESİ - BİLİMSEL ARAŞTIRMA PROJELERİ BİRİMİ

Project Number

19092

References

• Walkowska J, Zielinska N, Karauda P, Tubbs RS, Kurtys K, Olewnik Ł. The Pancreas and Known Factors of Acute Pancreatitis. J Clin Med 2022;11:5565.
• Peery AF, Crockett SD, Murphy CC, et al. Burden and Cost of Gastrointestinal, Liver, and Pancreatic Diseases in the United States: Update 2018. Gastroenterology 2019;156:254-272.e11.
• Rasineni K, Srinivasan MP, Balamurugan AN, et al. Recent advances in understanding the complexity of alcohol-induced pancreatic dysfunction and pancreatitis development. Biomolecules 2020;doi: 10.3390/biom10050669.
• Adjuto-Saccone M, Soubeyran P, Garcia J, et al. TNF-α induces endothelial-mesenchymal transition promoting stromal development of pancreatic adenocarcinoma. Cell Death Dis 2021;doi: 10.1038/S41419-021-03920-4.
• Jiménez-Maldonado A, Montero S, Lemus M, et al. Moderate and high intensity chronic exercise reduces plasma tumor necrosis factor alpha and increases the langerhans islet area in healthy rats. J Musculoskelet Neuronal Interact 2019;19:354–61. https://pubmed.ncbi.nlm.nih.gov/31475943/ (accessed November 5, 2022).
• van Duijneveldt G, Griffin MDW, Putoczki TL. Emerging roles for the IL-6 family of cytokines in pancreatic cancer. Clin Sci 2020;134:2091–115.
• Bava EP, George J, Tarique M, et al. Pirfenidone increases IL-10 and improves acute pancreatitis in multiple clinically relevant murine models. JCI Insight 2022;doi: 10.1172/JCI.INSIGHT.141108.
• Linnemann AK, Blumer J, Marasco MR, et al. Interleukin 6 protects pancreatic β cells from apoptosis by stimulation of autophagy. FASEB J 2017;31:4140–52.
• Komolafe O, Pereira SP, Davidson BR, Gurusamy KS. Serum C-reactive protein, procalcitonin, and lactate dehydrogenase for the diagnosis of pancreatic necrosis. Cochrane Database Syst Rev 2017;doi: 10.1002/14651858.CD012645.
• Zheng Z, Huang G, Gao T, et al. Epigenetic Changes Associated With Interleukin-10. Front Immunol 2020;11:1105.
• McMichael EL, Jaime-Ramirez AC, Guenterberg KD, et al. IL-21 enhances natural killer cell response to cetuximab-coated pancreatic tumor cells. Clin Cancer Res 2017;23:489–502.
• Jakubowska MA, Ferdek PE, Gerasimenko O V., Gerasimenko J V., Petersen OH. Nitric oxide signals are interlinked with calcium signals in normal pancreatic stellate cells upon oxidative stress and inflammation. Open Biol 2016;doi: 10.1098/rsob.160149.
• Xu Y, Alfaro-Magallanes VM, Babitt JL. Physiological and pathophysiological mechanisms of hepcidin regulation: clinical implications for iron disorders. Br J Haematol 2021;193:882–93.
• Wang CY, Canali S, Bayer A, Dev S, Agarwal A, Babitt JL. Iron, erythropoietin, and inflammation regulate hepcidin in Bmp2-deficient mice, but serum iron fails to induce hepcidin in Bmp6-deficient mice. Am J Hematol 2019;94:240–8.
• Wang M, Phadke M, Packard D, Yadav D, Gorelick F. Zinc: Roles in pancreatic physiology and disease. Pancreatology 2020;20:1413–20.
• Vujasinovic M, Hedström A, Maisonneuve P, et al. Zinc deficiency in patients with chronic pancreatitis. World J Gastroenterol 2019;25:600–7.
• Kozłowska A, Wojtacha P, Majewski M, Równiak M. The cytokine alterations/abnormalities and oxidative damage in the pancreas during hypertension development. Pflugers Arch 2019;471:1331–40.
• Mei Q xiang, Hu J hui, Huang Z hua, et al. Pretreatment with chitosan oligosaccharides attenuate experimental severe acute pancreatitis via inhibiting oxidative stress and modulating intestinal homeostasis. Acta Pharmacol Sin 2021;42:942–53.
• Zeng L, Ai C, Zhang J, Zheng J. Essential element Cu and non-essential element Hg exposures have different toxicological effects in the liver of large yellow croaker. Mar Pollut Bull 2019;139:6–13.
• Arsenijevic T, Perret J, Van Laethem JL, Delporte C. Aquaporins Involvement in Pancreas Physiology and in Pancreatic Diseases. Int J Mol Sci 2019;doi: 10.3390/IJMS20205052.
• Granger DL, Taintor RR, Boockvar KS, Hibbs JB. Measurement of nitrate and nitrite in biological samples using nitrate reductase and Griess reaction. Methods Enzymol 1996;268:142–51.
• Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem 2004;37:277–85.
• Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005;38:1103–11.
• Song R, Yu D, Park J. Changes in gene expression of tumor necrosis factor alpha and interleukin 6 in a canine model of caerulein-induced pancreatitis. Can J Vet Res 2016;80:236.
• Kylänpää L, Rakonczay Z, O’Reilly DA. The clinical course of acute pancreatitis and the inflammatory mediators that drive it. Int J Inflam 2012;doi: 10.1155/2012/360685.
• Gasiorowska A, Talar-Wojnarowska R, Kaczka A, Borkowska A, Czupryniak L, Małecka-Panas E. Subclinical Inflammation and Endothelial Dysfunction in Patients with Chronic Pancreatitis and Newly Diagnosed Pancreatic Cancer. Dig Dis Sci 2016;61:1121–9.
• Keany KM, Fosgate GT, Perry SM, Stroup ST, Steiner JM. Serum concentrations of canine pancreatic lipase immunoreactivity and C-reactive protein for monitoring disease progression in dogs with acute pancreatitis. J Vet Intern Med 2021;35:2187–95.
• Beringer A, Thiam N, Molle J, Bartosch B, Miossec P. Synergistic effect of interleukin-17 and tumour necrosis factor-α on inflammatory response in hepatocytes through interleukin-6-dependent and independent pathways. Clin Exp Immunol 2018;193:221–33.
• Takahashi K, Nishida A, Shioya M, et al. Interleukin (IL)-1β Is a Strong Inducer of IL-36γ Expression in Human Colonic Myofibroblasts. PLoS One 2015;doi: 10.1371/JOURNAL.PONE.0138423.
• Lin WR, Lim SN, Yen TH, Alison MR. The Influence of Bone Marrow-Secreted IL-10 in a Mouse Model of Cerulein-Induced Pancreatic Fibrosis. Biomed Res Int 2016;doi: 10.1155/2016/4601532.
• Zhou X, Liu Z, Jang F, Xiang C, Li Y, He Y. Autocrine Sonic hedgehog attenuates inflammation in cerulein-induced acute pancreatitis in mice via upregulation of IL-10. PLoS One 2012;doi: 10.1371/JOURNAL.PONE.0044121.
• Linnebacher A, Mayer P, Marnet N, et al. Interleukin 21 Receptor/Ligand Interaction Is Linked to Disease Progression in Pancreatic Cancer. Cells 2019;doi: 10.3390/CELLS8091104.
• Sutherland APR, Belle T Van, Wurster AL, et al. Interleukin-21 is required for the development of type 1 diabetes in NOD mice. Diabetes 2009;58:1144–55.
• Andican G, Gelisgen R, Unal E, et al. Oxidative stress and nitric oxide in rats with alcohol-induced acute pancreatitis. World J Gastroenterol 2005;11:2340–5.
• Emerald BS, Mohsin S, D’souza C, et al. Diabetes Mellitus Alters the Immuno-Expression of Neuronal Nitric Oxide Synthase in the Rat Pancreas. Int J Mol Sci 2022;doi: 10.3390/IJMS23094974.
• Julián-Serrano S, Yuan F, Wheeler W, et al. Hepcidin-regulating iron metabolism genes and pancreatic ductal adenocarcinoma: a pathway analysis of genome-wide association studies. Am J Clin Nutr 2021;114:1408–17.
• Garg PK, Singh VP. Organ Failure Due to Systemic Injury in Acute Pancreatitis. Gastroenterology 2019;156:2008–23.
• Venglovecz V, Pallagi P, Kemény L V., et al. The Importance of Aquaporin 1 in Pancreatitis and Its Relation to the CFTR Cl- Channel. Front Physiol 2018;doi: 10.3389/FPHYS.2018.00854.
• Gao Z, Xu J, Sun D, et al. Traditional Chinese medicine, Qing Ying Tang, ameliorates the severity of acute lung injury induced by severe acute pancreatitis in rats via the upregulation of aquaporin-1. Exp Ther Med 2014;8:1819–24.
• Lener MR, Scott RJ, Wiechowska-Kozłowska A, et al. Serum Concentrations of Selenium and Copper in Patients Diagnosed with Pancreatic Cancer. Cancer Res Treat 2016;48:1056–64.
• Zheng X;, Zhao J;, Llorent-Martínez EJ, et al. Research Progress of Antioxidant Nanomaterials for Acute Pancreatitis. Mol 2022, Vol 27, Page 7238 2022;27:7238.
• Esrefoglu M. Experimental and clinical evidence of antioxidant therapy in acute pancreatitis. World J Gastroenterol 2012;18:5533–41.
• L R, ND V, H I. Role of Oxidative Stress in the Pathogenesis of Pancreatitis: Effect of Antioxidant Therapy. Pancreat Disord Ther 2013;doi: 10.4172/2165-7092.1000112.