Antioxidant Effects of Epigallocatechin Gallate in Cerulein-Induced Pancreatitis

Year 2019, Volume: 78 Issue: 2, 125 - 132, 06.12.2019

Elif Karacaoglu Gozde Girgin Guldeniz Selmanoglu Terken Baydar

Abstract

Objective: Acute pancreatitis (AP) is an inflammatory disease of the pancreas resulting from auto-activation of digestive enzymes and damage to the pancreatic parenchyma. Reactive oxygen species (ROS) play an important role in the progression of AP. In the present study, we aimed to evaluate epigallocatechin-3 gallate (EGCG) in reducing the inflammatory reaction and tissue damage in experimental AP rat model. Materials and Methods: Amylase, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels were measured. Histopathological, immunohistochemical analyses of apoptotic cells, CD-8α and CD-68 were performed. Superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST) were determined in hemolysates. Results: Cerulein+EGCG treatment did not cause decreases in the amylase levels. IL-6 levels decreased in cerulein+EGCG group, however, TNF-α levels increased. No changes were observed in SOD activity by EGCG treatment, CAT and GST activities increased. EGCG treatment caused severe edema, inflammation and fat necrosis after cerulein-induced pancreatitis. Apoptosis in pancreas, CD8-α and CD-68 positive cells increased in EGCG treatment after pancreatitis induction. Conclusion: It may be suggested that EGCG showed a pro-oxidant effect, in contrast to the expected in the pancreatitis model when compared to a positive control. It can be concluded that overconsumption of EGCG should be avoided in pancreatitis conditions. 

Keywords

Acute Pancreatitis, Reactive Oxygen Species, Epigallocatechin-3 Gallate, N-acetylcysteine, Antioxidant Effect

Supporting Institution

This study was financialiy supported by the Hacettepe University Research Projects Coordination Unit.

Project Number

09 D03 301 001

References

• 1. Lei QC, Wang XY, Xia XF, Zheng HZ, Bi JC, Tian F, et al. The role of omega-3 fatty acids in acute pancreatitis: A meta-analysis of randomized controlled trials. Nutrients 2015; 7(4): 2261-73.
• 2. Jha RK, Ma Q, Sha H, Palikhe M. Acute pancreatitis: a literature review. Med Sci Mon 2009; 15(7): RA147-RA56.
• 3. Aranda-Narváez JM, González-Sánchez AJ, Montiel-Casado MC, Titos-García A, Santoyo-Santoyo J. Acute necrotizing pancreatitis: surgical indications and technical procedures. World J Clin Cases 2014; 2(12): 840.
• 4. Elfar M, Gaber LW, Sabek O, Fischer CP, Gaber AO. The inflammatory cascade in acute pancreatitis: relevance to clinical disease. Surg Clin North Am 2007; 87(6): 1325-40.
• 5. Saruç M, Yuceyar H, Turkel N, Ozutemiz O, Tuzcuoglu I, Ayhan S, et al. The role of heme in hemolysis-induced acute pancreatitis. Med Sci Mon 2007; 13(3): BR67-BR72.
• 6. Wei M, Gong Y-J, Tu L, Li J, Liang Y-H, Zhang Y-H. Expression of phosphatidylinositol-3 kinase and effects of inhibitor wortmannin on expression of tumor necrosis factor-a in severe acute pancreatitis associated with acute lung injury. World J Emerg Med 2015; 6(4): 299.
• 7. De Campos T, Deree J, Coimbra R. From acute pancreatitis to endorgan injury: mechanisms of acute lung injury. Surgical Infect 2007; 8(1): 107-20.
• 8. Mokra D, Kosutova P. Biomarkers in acute lung injury. Respir Physiol Neurobiol 2015; 209: 52-8.
• 9. Tsuji N, Watanabe N, Okamoto T, Niitsu Y. Specific interaction of pancreatic elastase and leucocytes to produce oxygen radicals and its implication in pancreatitis. Gut 1994; 35(11): 1659-64.
• 10. Yu JH, Kim H. Oxidative stress and inflammatory signaling in cerulein pancreatitis. World journal of gastroenterology: WJG 2014; 20(46): 17324.
• 11. Babu BI, Malleo G, Genovese T, Mazzon E, Di Paola R, Crisafulli C, et al. Green tea polyphenols ameliorate pancreatic injury in ceruleininduced murine acute pancreatitis. Pancreas 2009; 38(8): 954-67.
• 12. Su KH, Cuthbertson C, Christophi C. Review of experimental animal models of acute pancreatitis. HPB (Oxford). 2006; 8(4): 264-86.
• 13. Pandey KB, Rizvi SI. Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longev 2009; 2(5): 270-8.
• 14. Shay J, Elbaz HA, Lee I, Zielske SP, Malek MH, Hüttemann M. Molecular mechanisms and therapeutic effects of (−)-epicatechin and other polyphenols in cancer, Inflammation, Diabetes, and Neurodegeneration. Oxid Med Cell Longev 2015; 2015.
• 15. Erguder IB, Avci A, Devrim E, Durak I. Effects of cooking techniques on antioxidant enzyme activities of some fruits and vegetables. Turk J Med Sci 2007; 37(3): 151-6.
• 16. Mekiňová D, Chorvathova V, Volkovova K, Staruchova M, Graňičová E, Klvanova J, et al. Effect of intake of exogenous vitamins C, E and Β‐carotene on the antioxidative status in kidneys of rats with streptozotocin‐induced diabetes. Mol Nutr Food Res 1995; 39(4): 257-61.
• 17. Süloğlu AK, Girgin G, Selmanoğlu G, Balcı S, Baydar T. Possible effects of lycopene and silymarin on rat liver functions and oxidative stress markers. Turk J Biochem/Turk Biyokim Derg 2014; 39(3):344-50.
• 18. Sureda A, Tejada S, Del Mar Bibiloni M, Antoni Tur J, Pons A. Polyphenols: well beyond the antioxidant capacity: polyphenol supplementation and exercise-induced oxidative stress and inflammation. Curr Pharm Biotechnol 2014; 15(4): 373-9.
• 19. Lambert JD, Elias RJ. The antioxidant and pro-oxidant activities of green tea polyphenols: a role in cancer prevention. Arch Biochem Biophys 2010; 501(1): 65-72.
• 20. Lin C-H, Chao L-K, Hung P-H, Chen Y-J. EGCG inhibits the growth and tumorigenicity of nasopharyngeal tumor-initiating cells through attenuation of stat3 activation. Int J Clin Exp Pathol 2014; 7(5): 2372.
• 21. Yu H, Pardoll D, Jove R. Stats in cancer inflammation and immunity: a leading role for stat3. Nat Rev Cancer 2009; 9(11): 798-809.
• 22. Mukherjee S, Siddiqui MA, Dayal S, Ayoub YZ, Malathi K. Epigallocatechin-3-gallate suppresses proinflammatory cytokines and chemokines induced by toll-like receptor 9 agonists in prostate cancer cells. J Inflamm Res 2014; 7: 89.
• 23. Ramudo L, Manso MA. N-acetylcysteine in acute pancreatitis. World J Gastrointest Pharmacol Ther 2010; 1(1): 21.
• 24. Muià C, Mazzon E, Di Paola R, Genovese T, Menegazzi M, Caputi AP, et al. Green tea polyphenol extract attenuates ischemia/reperfusion injury of the gut. Naunyn-Schmiedebergs Arch Pharmacol 2005; 371(5): 364-74.
• 25. Senthil Kumaran V, Arulmathi K, Srividhya R, Kalaiselvi P. Repletion of antioxidant status by EGCG and retardation of oxidative damage induced macromolecular anomalies in aged rats. Exp Gerontol 2008; 43(3): 176-83.
• 26. Meng M, Li Y-Q, Yan M-X, Kou Y, Ren H-B. Effects of epigallocatechin gallate on diethyldithiocarbamate-induced pancreatic fibrosis in rats. Biol Pharm Bull 2007; 30 (6): 1091-6.
• 27. Abdallah MF, Karacaoglu E, Girgin G, Kilicarslan B, Selmanoglu G, Baydar T. Influence of subacute melatonin treatment on antioxidant factors in the liver of female rats. J Exp App Anim Sci 2015; 1(3): 359-68.
• 28. Yagci G, Gul H, Simsek A, Buyukdogan V, Onguru O, Zeybek N, et al. Beneficial effects of N-acetylcysteine on sodium taurocholateinduced pancreatitis in rats. J Gastroenterol 2004; 39(3): 268-76.
• 29. Kim H. Cerulein pancreatitis: oxidative stress, inflammation, and apoptosis. Gut Liver 2008; 2(2): 74-80.
• 30. Hyun JJ, Lee HS. Experimental models of pancreatitis. Clin Endosc 2014; 47(3): 212-6.
• 31. Rodrigo R, Gil-Becerra D. Chapter 17 - Implications of polyphenols on endogenous antioxidant defense systems in human diseases. Polyphenols in Human Health and Disease. San Diego: Academic Press; 2014. p. 201-17.
• 32. Fukui M, Kanoh M, Takamatsu Y, Arakawa Y. Analysis of serum catalase activities in pancreatic diseases. J Gastroenterol 2004; 39(5): 469-74.
• 33. Rahman SH, Ibrahim K, Larvin M, Kingsnorth A, Mcmahon MJ. Association of antioxidant enzyme gene polymorphisms and glutathione status with severe acute pancreatitis. Gastroenterology 2004; 126(5): 1312-22.
• 34. Pérez S, Pereda J, Sabater L, Sastre J. Redox Signaling in acute pancreatitis. Redox Biol 2015; 5: 1-14.
• 35. Gomez-Cambronero LG, Sabater L, Pereda J, Cassinello N, Camps B, Vina J, et al. Role of cytokines and oxidative stress in the pathophysiology of acute pancreatitis: therapeutical implications. Curr Drug Targets Inflamm Allergy 2002; 1(4): 393-403.
• 36. Mayer J, Rau B, Gansauge F, Beger HG. Inflammatory mediators in human acute pancreatitis: clinical and pathophysiological implications. Gut 2000; 47(4): 546-52.
• 37. Javier E, Javier P, Alessandro A, Juan S, Luis S, Luis A, et al. Role of redox Signaling, protein phosphatases and histone acetylation in the inflammatory cascade in acute pancreatitis: therapeutic implications. Inflamm Allergy Drug Targets 2010; 9(2): 97-108.
• 38. Xue J, Sharma V, Hsieh MH, Chawla A, Murali R, Pandol SJ, et al. Alternatively activated macrophages promote pancreatic fibrosis in chronic pancreatitis. Nat Commun 2015; 6: 7158.
• 39. Gukovskaya AS, Gukovsky I, Zaninovic V, Song M, Sandoval D, Gukovsky S, et al. Pancreatic acinar cells produce, release, and respond to tumor necrosis factor-alpha. Role in regulating cell death and pancreatitis. J Clin Invest 1997; 100(7): 1853-62.
• 40. Elbling L, Weiss R-M, Teufelhofer O, Uhl M, Knasmueller S, SchulteHermann R, et al. Green tea extract and (–)-epigallocatechin-3-gallate, the major tea catechin, exert oxidant but lack antioxidant activities. The FASEB J 2005; 19(7): 807-09.
• 41. Yang G-Y, Liao J, Li C, Chung J, Yurkow EJ, Ho C-T, et al. Effect of black and green tea polyphenols on c-Jun phosphorylation and H2O2 production in transformed and non-transformed human bronchial cell lines: possible mechanisms of cell growth inhibition and apoptosis induction. Carcinogenesis 2000; 21(11): 2035-9.
• 42. Qanungo S, Das M, Haldar S, Basu A. Epigallocatechin-3-gallate induces mitochondrial membrane depolarization and caspasedependent apoptosis in pancreatic cancer cells. Carcinogenesis 2005; 26(5): 958-67.
• 43. Hayakawa F, Ishizu Y, Hoshino N, Yamaji A, Ando T, Kimura T. Prooxidative activities of tea catechins in the presence of Cu2+. Biosci Biotechnol Biochem 2004; 68(9): 1825-30.
• 44. Preedy VR. Tea in health and disease prevention: Academic Press; 2012.