Deneysel Pankreatitte Oksidatif Stres ve Lipid Peroksidasyon Durumunun Değerlendirilmesi

Yıl 2022, Cilt: 6 Sayı: 1, 24 - 30, 28.04.2022

Hakan Balbaloğlu , Güldeniz Karadeniz Çakmak , İshak Özel Tekin , Şerefden Açıkgöz , Burak Bahadır , Öge Taşcılar

https://doi.org/10.29058/mjwbs.1073764

Öz

Amaç: Günümüzde, halen akut pankreatit patogenezi tartışma konusu olmaya devam etmektedir. Çalışmamız, taurokolata ile oluşturulan deneysel akut pankreatit modelinde oksidatif stres ve lipid peroksidasyon durumunu araştırmayı amaçlamaktadır. Araştırmamızda oksidatif stresin biyobelirteçi olarak, okside LDL'yi kullandık.
Gereç ve Yöntemler: Çalışmamızda dört gruba ayrılmış yirmi altı Wistar albino sıçan kullandık. Sham gurubu, kontrol grubu (grup 1) ve sodyum taurokolata ile akut pankreatit oluşturulan deney grubu; 24. saatte (grup 2), 48. saatte (grup 3) ve 72. saatte (grup 4) sakrifiye edildi. Pankreas dokusu malondialdehit (MDA) düzeylerini lipid peroksidasyonunun bir göstergesi olarak değerlendirdik. İmmünofloresan boyama kullanarak pankreas dokularında ox-LDL varlığını belirledik ve pankreas dokularının histopatolojik analizi ile karşılaştırdık.
Bulgular: Pankreas dokusunda MDA ve serum amilaz, ALT ve AST düzeylerinin grup 2, 3 ve 4'te anlamlı olarak yüksek olduğunu ve histopatolojik bulgularının da pankreatit ile uyumlu olduğunu gördük. Histopatolojik bulgular ile ox-LDL birikim düzeyini karşılaştırdık ve Grup 2, 3 ve 4'te pankreas dokusunda ox-LDL birikimi düzeyi ile pankreatit şiddeti arasında paralellik bulduk.
Sonuç: Bu çalışma, taurokolata bağlı akut pankreatit modelinde pankreas dokusunda ox-LDL moleküllerinin birikimini göstermektedir. Ox-LDL dahil olmak üzere bu yan ürünlere göre, tedavi modalitelerinin akut pankreatitin lokal değil sistemik komplikasyonlarını iyileştirmede faydalı etkileri olabileceğini düşünüyoruz.

Anahtar Kelimeler

deneysel pankreatit, ; oksidatif stres, lipid peroksidasyonu, okside düşük yoğunluklu lipoprotein, malondialdehit.

The Evaluation of Oxidative Stress and Lipid Peroxidation Status in Experimental Pancreatitis

Öz

Aim/Background: Currently, acute pancreatitis pathogenesis remains a matter of debate. Our study aims to investigate the oxidative stress and lipid peroxidation state in taurocholate-induced acute pancreatitis, and we used oxidized LDL as a biomarker of oxidative stress.
Methods: We used twenty-six Wistar albino rats divided into four groups. Sham-operated rats, control group (group 1), and experimental group with sodium taurocholate-induced acute pancreatitis; were sacrificed at 24 hours (group 2), 48 hours (group 3), and 72 hours (group 4). We evaluated pancreatic tissue malondialdehyde (MDA) levels as an indicator of lipid peroxidation. Then, using the immunofluorescence staining, we determined the presence of ox-LDL in pancreatic tissues, which we used to compare the histopathological analysis of pancreatitis.
Results: We found that MDA levels in pancreatic tissue and serum amylase, ALT, and AST were significantly higher in groups 2, 3, and 4. Histopathological findings of groups 2, 3, and 4 were compatible with pancreatitis, and we encountered the level of ox-LDL accumulation. We found a parallelism between the level of ox-LDL accumulation in pancreatic tissue and the severity of pancreatitis in groups 2, 3, and 4.
Conclusion: This study demonstrates the accumulation of ox-LDL molecules in pancreatic tissue in a taurocholate-induced acute pancreatitis model. According to these byproducts, including ox-LDL, we conceive that treatment modalities might have beneficial effects in improving not local but systemic complications of acute pancreatitis.

Anahtar Kelimeler

experimental pancreatitis, oxidative stress, lipid peroxidation, oxidized low-density lipoprotein, malondialdehyde

Kaynakça

• References 1. Lippi G, Valentino M, Cervellin G. Laboratory diagnosis of acute pancreatitis: in search of the Holy Grail. Critical Reviews in Clinical Laboratory Sciences 2012; 1: 18-31.
• 2. Lankisch PG, Apte M, Banks PA. Acute pancreatitis. Lancet 2015; 386: 85-96.
• 3. Bulkley GB. The role of oxygen free radicals in human disease processes. Surgery 1983; 94(3): 407-11.
• 4. Park B, Chung J, Lee J, et al. Role of oxygen free radicals in patients with acute pancreatitis. World J Gastroenterol 2003; 9(10): 2266-9.
• 5. Que RS, Cao LP, Ding GP, Hu JA, Mao KJ, Wang GF. Correlation of nitric oxide and other free radicals with the severity of acute pancreatitis and complicated systemic inflammatory response syndrome. Pancreas 2010; 39(4): 536-40.
• 6. Özcan O, Erdal H, Çakırca G, Yönden Z. Oxidative stress and its impacts on intracellular lipids, proteins and DNA. J Clin Exp Investig 2015; 6(3): 331-6.
• 7. Gasparovic AC, Jaganjac M, Mihaljevic B, Sunjic SB, Zarkovic N. Assays for the measurement of lipid peroxidation. Methods Mol Biol 2013; 965: 283-93.
• 8. Tsimikas S, Witztum JL. The oxidative modification hypothesis of atherogenesis. Oxidative Stress and Vascular Disease. 1st ed. Boston, Springer 2000. 49-74.
• 9. Kamps JA, Kruijt JK, Kuiper J, van Berkel TJ. Characterization of the interaction of acetylated LDL and oxidatively modified LDL with human liver parenchymal and Kupffer cells in culture. Arterioscler Thromb A J Vasc Biol 1992; 12(9): 1079-87.
• 10. Schmidt J, Rattner D, Lewandrowski K, et al. A better model of acute pancreatitis for evaluating therapy. Ann Surg 1992; 215(1): 44-56.
• 11. Uchiyama M, Mihara M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem 1978; 86(1): 271-8.
• 12. Armstrong J, Cash N, Soares P, Souza M, Sutton R, Criddle D. Oxidative stress in acute pancreatitis: lost in translation?. Free Radic Res 2013; 47(11): 917-33.
• 13. Leung P, Chan Y. Role of oxidative stress in pancreatic inflammation. Antioxid Redox Signal 2009; 11(1): 135-65.
• 14. Tsai L, Lee K, Liu T. Evidence for accelerated generation of hydroxyl radicals in experimental obstructive jaundice of rats. Free Radic Biol Med 1998; 24(5): 732-7.
• 15. Yan L, Sohal R. Mitochondrial adenine nucleotide translocase is modified oxidatively during aging. Proc Natl Acad Sci U S A 1998; 95(22): 12896-901.
• 16. Yan LJ. Positive oxidative stress in aging and aging-related disease tolerance. Redox Biol 2014; 2(1): 165-9.
• 17. Dokuyucu R, Karateke A, Gokce H, et al. Antioxidant effect of erdosteine and lipoic acid in ovarian ischemia-reperfusion injury. Eur J Obstet Gynecol Reprod Biol 2014; 183: 23-7.
• 18. Berlett BS, Stadtman ER. Protein oxidation in aging, disease, and oxidative stress. The Journal of Biological Chemistry 1997; 272(33): 20313-16.
• 19. Gupta R, Patel A, Shah N, et al. Oxidative stress and antioxidants in disease and cancer: a review. Asian Pac J Cancer Prev 2014; 15(11): 4405-9.
• 20. Afek A, George J, Gilburd B, et al. Immunization of low-density lipoprotein receptor deficient (LDL-RD) mice with heat shock protein 65 (HSP-65) promotes early atherosclerosis. J Autoimmun 2000; 14(2): 115-21.
• 21. Marathe G, Davies S, Harrison K, et al. Inflammatory platelet-activating factor-like phospholipids in oxidized low density lipoproteins are fragmented alkyl phosphatidylcholines. J Biol Chem 1999; 274(40): 28395-404.
• 22. Feng Y, Schreiner GF, Chakravarty S, Liu DY, Joly AH. Inhibition of the mitogen activated protein kinase, p38α, prevents proinflammatory cytokine induction by human adherent mononuclear leukocytes in response to lipid loading. Atherosclerosis 2001; 158(2): 331-8.
• 23. Hsu HY, Chiu SL, Wen MH, Chen KY, Hua KF. Ligands of Macrophage Scavenger Receptor Induce Cytokine Expression via Differential Modulation of Protein Kinase Signaling Pathways. J Biol Chem 2001; 276(31): 28719-30.
• 24. Aboutwerat A, Pemberton P, Smith A, et al. Oxidant stress is a significant feature of primary biliary cirrhosis. Biochim Biophys Acta - Mol Basis Dis 2003; 1637(2): 142-50.
• 25. Kudari A, Wig J, Vaiphei K, et al. Histopathological sequential changes sodium taurocholate-induced acute pancreatitis. J Pancreas 2007; 8(5): 564-72.
• 26. Schoenberg MH, Büchler M, Helfen M, Beger HG. Role of oxygen radicals in experimental acute pancreatitis. Eur Surg Res 1992; 24(1): 74-84.
• 27. Tsai K, Wang S, Chen T, et al. Oxidative stress: An important phenomenon with pathogenetic significance in the progression of acute pancreatitis. Gut 1998; 42(6): 850-5.