Abstract
Many studies suggest that Epigallocatechin-3-Gallate (EGCG) has many protective effects. But little is known about its protective effects against chronic restraint stress-induced damage in rats. The aim was to demonstrate the potential protective effects of EGCG against harmful pancreatic damage to the immobilization stress in the rat model. Forty rats, 2 months old, were divided into four groups (n = 10): control group; EGCG group, rats received EGCG by gavage (100 mg/kg /day) for 30 days; stressed group, rats exposed to immobilization stress; and stressed with EGCG group, rats exposed to immobilization stress and received EGCG for 30 days. Glycemic status parameters, corticosterone, and inflammatory markers were investigated on the first day, 15th day, and the 30th day of the experiment. Pancreatic oxidative stress markers and cytokines were evaluated. Histological, immunohistological, and statistical studies were performed. On the 15th day, fasting blood glucose (FBG), fasting plasma insulin (FPI), homeostatic model assessment for insulin resistance (HOMA-IR), and fasting plasma corticosterone were significantly higher in the stressed group when compared with first and 30th day in the same group as well as when compared with control and stressed with EGCG groups. The stressed group revealed significantly higher pancreatic IL-1β, IL-6, TNF-α, MDA, and NO, serum amylase and serum lipase, and significantly lower GSH, SOD, and CAT when compared to control and stressed with EGCG groups. EGCG treatment attenuated the pancreatic stress-induced cellular degeneration, leucocytic infiltration, and cytoplasmic vacuolations; significantly decreased area percentage of collagen fibers; and significantly increased mean area percentage of insulin immunopositive cell as compared with stressed group. EGCG is a protective agent against immobilization stress because of its anti-diabetic, anti-inflammatory, and and anti-oxidative stress properties, as confirmed by biochemical and histological alterations.
Similar content being viewed by others
References
Aneja R, Hake PW, Burroughs TJ et al (2004) Epigallocatechin, a green tea polyphenol, attenuates myocardial ischemia- reperfusion injury in rats. Mol Med 10(1-6):5–62
Babu PV, Liu D (2008) Green tea catechins and cardiovascular health: an update. Curr Med Chem 15(18):1840–1850
Bali A, Jaggi AS (2013) Angiotensin as stress mediator: role of its receptor and interrelationships among other stress mediators and receptors. Pharmacol Res 76:49–57
Bancroft J, Gamble M (2008) Theory and practice of histological techniques. staining methods, 7th ed.,Churchill Livingstone, Edinburgh, London, Madrid, Melbourne, New York, and Tokyo 263 -325
Beck IT (1973) The role of pancreatic enzymes in digestion. Am J Clin Nutr 26:311–325
Binker MG, Cosen-Binker LI (2014) Acute pancreatitis: the stress factor. World J Gastroenterol 20:5801–5807
Binker MG, Binker-Cosen AA, Richards D, Gaisano HY, de Cosen RH, Cosen-Binker LI (2010) Chronic stress sensitizes rats to pancreatitis induced by cerulein: role of TNF-α. World J Gastroenterol 16(44):5565–5581
Birari RB, Bhutani KK (2007) Pancreatic lipase inhibitors from natura sources: unexplored potential. Drug Discov Today 12:879–889
Bitgul G, Tekmen I, Keles D et al (2013) Protective effects of resveratrol against chronic immobilization stress on testis. ISRN Urol. 278720
Carroll JK, Herrick B, Gipson T et al (2007) Acute pancreatitis: diagnosis, prognosis, and treatment. Am Fam Physician:75
Chen J, Du L, Li J et al (2016) Epigallocatechin-3-gallate attenuates cadmium-induced chronic renal injury and fibrosis. Food Chem Toxicol 96:70–78
Cho HH, Han DW, Matsumura K et al (2008) The behavior of vascular smooth muscle cells and platelets onto epigallocatechin gallate-releasing poly (l-lactide-co-ε-caprolactone) as stent-coating materials. Biomaterials 29(7):884–893
Crestani CC (2016) Emotional stress and cardiovascular complications in animal models: a review of the influence of stress type. Front Physiol 7:251
Czakó L, Hegyi P, Rakonczay Z Jr et al (2009) Interactions between the endocrine and exocrine pancreas and their clinical relevance. Pancreatology 9(4):351–359
Date K, Satoh A, Iida K, Ogawa H (2015) Pancreatic α-amylase controls glucose assimilation by duodenal retrieval through n-glycan-specific binding, endocytosis, and degradation. J Biol Chem 290(28):17439–17450
de Boer SF, van der Gugten J, Slangen JL (1989) Plasma catecholamine and corticosterone responses to predictable and unpredictable noise stress in rats. Physiol Behav 45(4):789–795
Dickinson D, DeRossi S, Yu H, Thomas C, Kragor C, Paquin B, Hahn E, Ohno S, Yamamoto T, Hsu S (2014) Epigallocatechin-3-gallate modulates antioxidant defense enzyme expression in murine submandibular and pancreatic exocrine gland cells and human HSG cells. Autoimmunity 47:177–184
Elbassuoni EA, Abdel Hafez SM (2019) Impact of chronic exercise on counteracting chronic stress-induced functional and morphological pancreatic changes in male albino rats. Cell Stress Chaperones 24:567–580
Elbling L, Herbacek I, Weiss RM, Jantschitsch C, Micksche M, Gerner C, Pangratz H, Grusch M, Knasmüller S, Berger W (2010) Hydrogen peroxide mediates EGCG-induced antioxidant protection in human keratinocytes. Free Radic Biol Med 49(9):1444–1452
Fonseca SG, Urano F, Burcin M, Gromada J (2010) Stress hypERactivation in the β-cell. Islets 2:1–9
Forester SC, Gu Y, Lambert JD (2012) Inhibition of starch digestion by the green tea polyphenol, (-)-epigallocatechin-3-gallate. Mol Nutr Food Res 56(11):1647–1654
Godoy LD, Rossignoli MT, Delfino-Pereira P, Garcia-Cairasco N, de Lima Umeoka EH (2018) A comprehensive overview on stress neurobiology: basic concepts and clinical implications. Front Behav Neurosci 12:127
Gonchar OO, Maznychenko AV, Bulgakova NV et al (2018) C60 fullerene prevents restraint stress-induced oxidative disorders in rat tissues: possible involvement of the Nrf2/ARE-antioxidant pathway. Oxidative Med Cell Longev 2518676
Herman JP (2013) Neural control of chronic stress adaptation. Front Behav Neurosci 7:61
Hintzpeter J, Stapelfeld C, Loerz C et al (2014) Green tea and one of its constituents, Epigallocatechine-3-gallate, are potent inhibitors of human 11β-hydroxysteroid dehydrogenase type 1. PLoS One 9(1):e84468
Hsieh SR, Tsai DC, Chen JY, Tsai SW, Liou YM (2009) Green tea extract protects rats against myocardial infarction associated with left anterior descending coronary artery ligation. Pflugers Arch 458:631–642
Ikeda I, Tsuda K, Suzuki Y, Kobayashi M, Unno T, Tomoyori H, Goto H, Kawata Y, Imaizumi K, Nozawa A, Kakuda T (2005) Tea catechins with a galloyl moiety suppress postprandial hypertriacylglycerolemia by delaying lymphatic transport of dietary fat in rats. J Nutr 135:155–159
Kim IB, Kim DY, Lee SJ, Sun MJ, Lee MS, Li H, Cho JJ, Park CS (2006) Inhibition of IL-8 production by green tea polyphenols in human nasal fibroblasts and A549 epithelial cells. Biol Pharm Bull 29(6):1120–1125
Leibowitz SF, Wortley KE (2004) Hypothalamic control of energy balance: different peptides, different functions. Peptide 25:473–504
Lu C, Zhu W, Shen CL, Gao W (2012) Green tea polyphenols reduce body weight in rats by modulating obesity-related genes. PLoS One 7(6):e38332
Lutgendorff F, Trulsson LM, van Minnen LP et al (2008) Probiotics enhance pancreatic glutathione biosynthesis and reduce oxidative stress in acute experimental pancreatitis. Am J Phys 295:G1111–G1121
McEwen B (2000) The neurobiology of stress: from serendipity to clinical relevance. Brain Res 886:172–189
Miller AH, Maletic V, Raison CL (2009) Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry 65:732–741
Muniraj T, Dang S, Pitchumoni CS (2015) Pancreatitis or not?—elevated lipase and amylase in ICU patients. J Crit Care 30:1370–1375
Nakamuta M, Higashi N, Kohjima M, Fukushima M, Ohta S, Kotoh K, Kobayashi N, Enjoji M (2005) Epigallocatechin-3-gallate, a polyphenol component of green tea, suppresses both collagen production and collagenase activity in hepatic stellate cells. Int J Mol Med 16(4):677–681
Oishi K, Yokoi M, Maekawa S et al (1999) Oxidative stress and haematological changes in immobilized rats. Acta Physiol Scand 165:65–69
Pandol SJ, Gorelick FS, Lugea A (2011) Environmental and genetic stressors and the unfolded protein response in exocrine pancreatic function – a hypothesis. Front Physiol 2:8
Pathak NM, Millar PJB, Pathak V et al (2017) Beneficial metabolic effects of dietary epigallocatechin gallate alone and in combination with exendin-4 in high-fat diabetic mice. Mol Cell Endocrinol 460:200–208
Pham-Huy LA, He H, Pham-Huy C (2008) Free radicals, antioxidants in disease and health. Int J Biomed Sci 4(2):89–96
Pushparaj P, Tan C, Tan B (2000) Effects of Averrhoe bilimli leaf extract on blood glucose and lipids in streptozotocin-diabetic rats. J Ethnopharmacol 72:69–76
Roghani M, Tourandokht B (2010) Hypoglycemic and hypolipidemic effect and antioxidant activity of chronic epigallocatechin-gallate in streptozotocin-diabetic rats. Pathophysiology 17(1):55–59
Rohleder N, Aringer M, Boentert M (2012) Role of interleukin-6 in stress, sleep, and fatigue. Ann N Y Acad Sci 1261:88–96
Rostamkhani F, Zardooz H, Zahediasl S et al (2012) Comparison of the effects of acute and chronic psychological stress on metabolic features in rats. J Zhejiang Univ Sci B 13(11):904–912
Salehi A, Rabiei Z, Setorki M (2018) Effect of gallic acid on chronic restraint stress-induced anxiety and memory loss in male BALB/c mice. Iran J Basic Med Sci 21(12):1232–1237
Selye H (1936) A syndrome produced by diverse nocuous agents. Nature 138: July 4, page 32, and reprinted with permission, Selye H (1998) J Neuropsychiatry Clin Neurosci 10: 230-231
Shimizu M, Shirakami Y, Sakai H, Kubota M, Kochi T, Ideta T, Miyazaki T, Moriwaki H (2015) Chemopreventive potential of green tea catechins in hepatocellular carcinoma. Int J Mol Sci 16:6124–6139
Smith RC, Southwell-Keely J, Chesher D (2005) Should serum pancreatic lipase replace serum amylase as a biomarker of acute pancreatitis? ANZ J Surg 75:399–404
Soliman NBE (2012) Effect of chronic immobilization stress on the pancreatic structure and the possible protective role of testosterone administration in male albino rats. Egypt J Histology 35:448–457
Teague CR, Dhabhar FS, Barton RH, Beckwith-Hall B, Powell J, Cobain M, Singer B, McEwen BS, Lindon JC, Nicholson JK, Holmes E (2007) Metabonomic studies on the physiological effects of acute and chronic psychological stress in Sprague-Dawley rats. J Proteome Res 6(6):2080–2093
Torgerson JS, Hauptman J, Boldrin MN, Sjostrom L (2004) XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care 27:155–161
Voorhees JL, Tarr AJ, Wohleb ES, Godbout JP, Mo X, Sheridan JF, Eubank TD, Marsh CB (2013) Prolonged restraint stress increases IL-6, reduces IL-10, and causes persistent depressive-like behavior that is reversed by recombinant IL-10. PLoS One 8:e58488
Wallace TM, Levy JC, Mathews DR (2004) Use and abuse of HOMA modeling. Diabetes Care 27:1487–1495
Wasowicz W, Neve J, Peretz A (1993) Optimized steps in fluorometric determination of thiobarbituric acid-reactive substances in serum: importance of extraction pH and influence of sample preservation and storage. Clin Chem 39:2522–2526
Yan YX, Xiao HB, Wang SS, Zhao J, He Y, Wang W, Dong J (2016) Investigation of the relationship between chronic stress and insulin resistance in a chinese population. J Epidemiol 26(7):355–360
Youn HS, Lee JY, Saitoh SI, Miyake K, Kang KW, Choi YJ, Hwang DH (2006) Suppression of MyD88-and TRIF-dependent signaling pathways of Toll-like receptor by (−)-epigallocatechin-3-gallate, a polyphenol component of green tea. Biochem Pharmacol 72(7):850–859
Yu NH, Pei H, Huang YP, Li YF (2017) (-)-Epigallocatechin-3-Gallate inhibits arsenic-induced inflammation and apoptosis through suppression of oxidative stress in mice. Cell Physiol Biochem 41:1788–1800
Zaidi SM, Al-Qirim TM, Hoda N et al (2003) Modulation of restraint stress-induced oxidative changes in rats by antioxidant vitamins. J Nutr Biochem 14:633–636
Zardooz H, Zahedi AS, Naseri MG (2006a) Effect of chronic psychological stress on insulin release from rat isolated pancreatic islets. Life Sci 79(1):57–62
Zardooz H, Zahedi AS, Gharib et al (2006b) Effect of chronic restraint stress on carbohydrate metabolism in rat. Physiol Behav 89(3):373–378
Zardooz H, Zahedias S, Rostamkhani F et al (2012) Effects of acute and chronic psychological stress on isolated islets' insulin release. EXCLI J 11:163–175
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest statement
No conflict of interest
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Faheem, N.M., Ali, T.M. The counteracting effects of (-)-Epigallocatechin-3-Gallate on the immobilization stress-induced adverse reactions in rat pancreas. Cell Stress and Chaperones 26, 159–172 (2021). https://doi.org/10.1007/s12192-020-01165-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12192-020-01165-2