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Antioxidant, anti-inflammatory, and anti-fibrotic properties of olive leaf extract protect against L-arginine induced chronic pancreatitis in the adult male albino rat

  • Received : 2021.09.14
  • Accepted : 2022.03.21
  • Published : 2022.06.30

Abstract

Chronic pancreatitis (CP) is an inflammatory disease affects the pancreas with upcoming fibrosis and notable parenchymal destruction. CP poses a high risk for pancreatic carcinoma. The present study aimed to investigate, for the first time up to our knowledge, the effect of olive leaf extract on L-arginine induced CP with referral to some of its underlying mechanisms. Forty adult male albino rats were divided equally into four groups; control, olive leaf extract treated (200 mg/kg orally once daily), CP group (300 mg L-arginine/100 g body weight intraperitoneally, once daily for 3 weeks then every 3 days for the subsequent 3 weeks), and CP treated with olive leaf extract group. At the end of the experiment, body weight, serum glucose, serum insulin, homeostatic model assessment of insulin resistance (HOMA-IR), serum amylase and lipase as well as tissue superoxide dismutase (SOD), and malondialdehyde (MDA) levels were assessed. Pancreatic tissues were subjected to histological and immuno-histochemical studies. The CP group revealed significant decrease in body weight and increase in serum glucose, serum insulin, HOMA-IR score, serum amylase, and serum lipase levels. Significant increase in MDA level and decrease in SOD level were detected. Marked degenerative changes and fibrosis were detected. Upregulation of alpha smooth muscle actin (α-SMA), transforming growth factor beta (TGF-β), caspase-3, and interleukin-6 (IL-6) immunoreactions were implicated in CP pathogenesis. Olive leaf extract alleviated all the examined parameters via its-antioxidant, anti-inflammatory, and anti-fibrotic properties. Olive leaf extract can protect against CP and restore pancreatic functions.

Keywords

References

  1. Whitcomb DC, Frulloni L, Garg P, Greer JB, Schneider A, Yadav D, Shimosegawa T. Chronic pancreatitis: an international draft consensus proposal for a new mechanistic definition. Pancreatology 2016;16:218-24. https://doi.org/10.1016/j.pan.2016.02.001
  2. Hu FB. Globalization of diabetes: the role of diet, lifestyle, and genes. Diabetes Care 2011;34:1249-57. https://doi.org/10.2337/dc11-0442
  3. Otsuki M, Yamamoto M, Yamaguchi T. Animal models of chronic pancreatitis. Gastroenterol Res Pract 2010;2010:403295.
  4. Brock C, Nielsen LM, Lelic D, Drewes AM. Pathophysiology of chronic pancreatitis. World J Gastroenterol 2013;19:7231-40. https://doi.org/10.3748/wjg.v19.i42.7231
  5. Melki G, Laham L, Karim G, Komal F, Kumar V, Barham S, Grossman M, Kuru S, Mohamed H, Garris R, Baddoura W. Chronic pancreatitis leading to pancreatogenic diabetes presenting in diabetic ketoacidosis: a rare entity. Gastroenterology Res 2019;12:208-10.
  6. Zheng Z, Chen Y, Tan C, Ke N, Du B, Liu X. Risk of pancreatic cancer in patients undergoing surgery for chronic pancreatitis. BMC Surg 2019;19:83.
  7. Dong JY, Qin LQ, Zhang Z, Zhao Y, Wang J, Arigoni F, Zhang W. Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials. Am Heart J 2011;162:959-65. https://doi.org/10.1016/j.ahj.2011.09.012
  8. Meshram A, Srivastava N. Diverse potential and pharmacological studies of arginine. J Proteins Proteomics 2015;6:237-43.
  9. Malins LR, Cergol KM, Payne RJ. Peptide ligation-desulfurization chemistry at arginine. Chembiochem 2013;14:559-63. https://doi.org/10.1002/cbic.201300049
  10. Sharma S, Rana SV, Nada R, Malhotra S, Rana S, Bhasin DK. Wheatgrass (Triticum Aestivum): an effective anti-oxidant in L-arginine induced chronic pancreatitis model of rat: a dose dependent study. Imp J Interdiscip Res 2017;3:245-51.
  11. Braganza JM, Lee SH, McCloy RF, McMahon MJ. Chronic pancreatitis. Lancet 2011;377:1184-97. https://doi.org/10.1016/S0140-6736(10)61852-1
  12. Mayerle J, Hoffmeister A, Werner J, Witt H, Lerch MM, Mossner J. Chronic pancreatitis--definition, etiology, investigation and treatment. Dtsch Arztebl Int 2013;110:387-93.
  13. Apte MV, Pirola RC, Wilson JS. Pancreatic stellate cells: a starring role in normal and diseased pancreas. Front Physiol 2012;3:344.
  14. Tang D, Wang D, Yuan Z, Xue X, Zhang Y, An Y, Chen J, Tu M, Lu Z, Wei J, Jiang K, Miao Y. Persistent activation of pancreatic stellate cells creates a microenvironment favorable for the malignant behavior of pancreatic ductal adenocarcinoma. Int J Cancer 2013;132:993-1003. https://doi.org/10.1002/ijc.27715
  15. Pothula SP, Xu Z, Goldstein D, Pirola RC, Wilson JS, Apte MV. Key role of pancreatic stellate cells in pancreatic cancer. Cancer Lett 2016;381:194-200.
  16. Eidi A, Eidi M, Darzi R. Antidiabetic effect of Olea europaea L. in normal and diabetic rats. Phytother Res 2009;23:347-50. https://doi.org/10.1002/ptr.2629
  17. El SN, Karakaya S. Olive tree (Olea europaea) leaves: potential beneficial effects on human health. Nutr Rev 2009;67:632-8. https://doi.org/10.1111/j.1753-4887.2009.00248.x
  18. de Bock M, Derraik JG, Brennan CM, Biggs JB, Morgan PE, Hodgkinson SC, Hofman PL, Cutfield WS. Olive (Olea europaea L.) leaf polyphenols improve insulin sensitivity in middle-aged overweight men: a randomized, placebo-controlled, crossover trial. PLoS One 2013;8:e57622.
  19. Burja B, Kuret T, Janko T, Topalovic D, Zivkovic L, MrakPoljsak K, Spremo-Potparevic B, Zigon P, Distler O, Cucnik S, Sodin-Semrl S, Lakota K, Frank-Bertoncelj M. Olive leaf extract attenuates inflammatory activation and DNA damage in human arterial endothelial cells. Front Cardiovasc Med 2019;6:56.
  20. Boss A, Bishop KS, Marlow G, Barnett MP, Ferguson LR. Evidence to support the anti-cancer effect of olive leaf extract and future directions. Nutrients 2016;8:513.
  21. Al-Basher GI. Anti-fibrogentic and hepatoprotective potential of methanolic olive extract on cadmium induced toxicity in rats. Life Sci J 2018;15:1-11.
  22. Lin Z, Zheng LC, Zhang HJ, Tsang SW, Bian ZX. Anti-fibrotic effects of phenolic compounds on pancreatic stellate cells. BMC Complement Altern Med 2015;15:259.
  23. Lins PG, Marina Piccoli Pugine S, Scatolini AM, de Melo MP. In vitro antioxidant activity of olive leaf extract (Olea europaea L.) and its protective effect on oxidative damage in human erythrocytes. Heliyon 2018;4:e00805.
  24. Fredstrom SB, Jessurun J, Gallaher DD. Pancreatitis induced in rats by repetitive administration of L-arginine. Pancreas 2009;38:344-5. https://doi.org/10.1097/MPA.0b013e318184ff83
  25. Al-Attar AM, Abu Zeid IM. Effect of tea (Camellia sinensis) and olive (Olea europaea L.) leaves extracts on male mice exposed to diazinon. Biomed Res Int 2013;2013:461415.
  26. Al-Attar AM, Alsalmi FA. Effect of Olea europaea leaves extract on streptozotocin induced diabetes in male albino rats. Saudi J Biol Sci 2019;26:118-28. https://doi.org/10.1016/j.sjbs.2017.03.002
  27. Judzewitsch RG, Pfeifer MA, Best JD, Beard JC, Halter JB, Porte D Jr. Chronic chlorpropamide therapy of noninsulin-dependent diabetes augments basal and stimulated insulin secretion by increasing islet sensitivity to glucose. J Clin Endocrinol Metab 1982;55:321-8. https://doi.org/10.1210/jcem-55-2-321
  28. Foo AY, Bais R. Amylase measurement with 2-chloro-4-nitrophenyl maltotrioside as substrate. Clin Chim Acta 1998;272:137-47. https://doi.org/10.1016/S0009-8981(98)00009-6
  29. Haffter D, Meyer N, Scholer A, Gyr K. [Diagnostic value of the determination of serum amylase and serum lipase in suspected acute onset of acute or chronic pancreatitis]. Schweiz Med Wochenschr 1983;113:184-8. German.
  30. Kono Y. Generation of superoxide radical during autoxidation of hydroxylamine and an assay for superoxide dismutase. Arch Biochem Biophys 1978;186:189-95. https://doi.org/10.1016/0003-9861(78)90479-4
  31. Liu J, Xia Q, Zhang Q, Li H, Zhang J, Li A, Xiu R. Peroxisome proliferator-activated receptor-gamma ligands 15-deoxy-delta(12,14)-prostaglandin J2 and pioglitazone inhibit hydroxyl peroxide-induced TNF-alpha and lipopolysaccharide-induced CXC chemokine expression in neonatal rat cardiac myocytes. Shock 2009;32:317-24. https://doi.org/10.1097/SHK.0b013e31819c374c
  32. Koivukoski S. Assessing goblet cell metaplasia and expression of peptidase inhibitor 15 in mouse prostate tissue [Thesis]. Tampere: Tampere University; 2015.
  33. Christley RM. Power and error: increased risk of false positive results in underpowered studies. Open Epidemiol J 2010;3:16-9. https://doi.org/10.2174/1874297101003010016
  34. Valente R, Waldthaler A, Scandavini CM, Vujasinovic M, Del Chiaro M, Arnelo U, Lohr JM. Conservative treatment of chronic pancreatitis: a practical approach. Scand J Surg 2020;109:59-68.
  35. Ramakrishnan P, Loh WM, Gopinath SCB, Bonam SR, Fareez IM, Mac Guad R, Sim MS, Wu YS. Selective phytochemicals targeting pancreatic stellate cells as new anti-fibrotic agents for chronic pancreatitis and pancreatic cancer. Acta Pharm Sin B 2020;10:399-413. https://doi.org/10.1016/j.apsb.2019.11.008
  36. Khan FY, Matar I. Chylous ascites secondary to hyperlipidemic pancreatitis with normal serum amylase and lipase. World J Gastroenterol 2007;13:480-2. https://doi.org/10.3748/wjg.v13.i3.480
  37. Dasgupta T, Hebbel RP, Kaul DK. Protective effect of arginine on oxidative stress in transgenic sickle mouse models. Free Radic Biol Med 2006;41:1771-80.
  38. Zari TA, Al-Attar AM. Therapeutic effects of olive leaves extract on rats treated with a sublethal concentration of carbendazim. Eur Rev Med Pharmacol Sci 2011;15:413-26.
  39. Bombardo M, Chen R, Malagola E, Saponara E, Hills AP, Graf R, Sonda S. Inhibition of class I histone deacetylases abrogates tumor growth factor β expression and development of fibrosis during chronic pancreatitis. Mol Pharmacol 2018;94:793-801. https://doi.org/10.1124/mol.117.110924
  40. Geyikoglu F, Emir M, Colak S, Koc K, Turkez H, Bakir M, Hosseinigouzdagani M, Cerig S, Keles ON, Ozek NS. Effect of oleuropein against chemotherapy drug-induced histological changes, oxidative stress, and DNA damages in rat kidney injury. J Food Drug Anal 2017;25:447-59. https://doi.org/10.1016/j.jfda.2016.07.002
  41. Bello M, Basilio-Antonio L, Fragoso-Vazquez J, Avalos-Soriano A, Correa-Basurto J. Molecular recognition between pancreatic lipase and natural and synthetic inhibitors. Int J Biol Macromol 2017;98:855-68.
  42. Schneider E, Schmid-Kotsas A, Zhao J, Weidenbach H, Schmid RM, Menke A, Adler G, Waltenberger J, Grunert A, Bachem MG. Identification of mediators stimulating proliferation and matrix synthesis of rat pancreatic stellate cells. Am J Physiol Cell Physiol 2001;281:C532-43. https://doi.org/10.1152/ajpcell.2001.281.2.C532
  43. McCarroll JA, Naim S, Sharbeen G, Russia N, Lee J, Kavallaris M, Goldstein D, Phillips PA. Role of pancreatic stellate cells in chemoresistance in pancreatic cancer. Front Physiol 2014;5:141.
  44. Gong Z, Yuan Y, Lou K, Tu S, Zhai Z, Xu J. Mechanisms of Chinese herb emodin and somatostatin analogs on pancreatic regeneration in acute pancreatitis in rats. Pancreas 2002;25:154-60. https://doi.org/10.1097/00006676-200208000-00007
  45. Mews P, Phillips P, Fahmy R, Korsten M, Pirola R, Wilson J, Apte M. Pancreatic stellate cells respond to inflammatory cytokines: potential role in chronic pancreatitis. Gut 2002;50:535-41. https://doi.org/10.1136/gut.50.4.535
  46. Omary MB, Lugea A, Lowe AW, Pandol SJ. The pancreatic stellate cell: a star on the rise in pancreatic diseases. J Clin Invest 2007;117:50-9.
  47. Buchwalow I, Schnekenburger J, Tiemann K, Samoilova V, Bankfalvi A, Poremba C, Schleicher C, Neumann J, Boecker W. L-arginine-NO-cGMP signalling pathway in pancreatitis. Sci Rep 2013;3:1899.
  48. Abdin AA, El-Hamid MA, El-Seoud SH, Balaha MF. Effect of pentoxifylline and/or alpha lipoic acid on experimentally induced acute pancreatitis. Eur J Pharmacol 2010;643:289-96. https://doi.org/10.1016/j.ejphar.2010.06.020
  49. Al-Azzawie HF, Alhamdani MS. Hypoglycemic and antioxidant effect of oleuropein in alloxan-diabetic rabbits. Life Sci 2006;78:1371-7. https://doi.org/10.1016/j.lfs.2005.07.029
  50. Abd El-Azim AO. Antioxidant effect of olive leaf extract on methotrexate-induced hepatic injury in rats. Canadian J Clin Nutr 2014;2:4-14. https://doi.org/10.14206/canad.j.clin.nutr.2014.01.02
  51. Al-Attar AM, Shawush NA. Influence of olive and rosemary leaves extracts on chemically induced liver cirrhosis in male rats. Saudi J Biol Sci 2015;22:157-63. https://doi.org/10.1016/j.sjbs.2014.08.005
  52. Lobo V, Patil A, Phatak A, Chandra N. Free radicals, antioxidants and functional foods: impact on human health. Pharmacogn Rev 2010;4:118-26. https://doi.org/10.4103/0973-7847.70902
  53. Cohen Z, Wilson J, Ritter L, McDonagh P. Caspase inhibition decreases both platelet phosphatidylserine exposure and aggregation: caspase inhibition of platelets. Thromb Res 2004;113:387-93. https://doi.org/10.1016/j.thromres.2004.03.020
  54. Mohammed HA, Okail HA, Ibrahim MA, Emam NM. Influences of olive leaf extract in the kidney of diabetic pregnant mice and their offspring. J Basic Appl Zool 2018;79:1-13. https://doi.org/10.1186/s41936-018-0014-x
  55. Pretnar-Oblak J, Sabovic M, Vidmar G, Zaletel M. Evaluation of L-arginine reactivity in comparison with flow-mediated dilatation and intima-media thickness. Ultrasound Med Biol 2007;33:1546-51. https://doi.org/10.1016/j.ultrasmedbio.2007.04.011
  56. Badr A, Fouad D. Anti-apoptotic and anti-inflammatory effects of olive leaf extract against cisplatin-induced nephrotoxicity in male rats. Int J Pharmacol 2016;12:675-88. https://doi.org/10.3923/ijp.2016.675.688
  57. Rahman SH, Ammori BJ, Larvin M, McMahon MJ. Increased nitric oxide excretion in patients with severe acute pancreatitis: evidence of an endotoxin mediated inflammatory response? Gut 2003;52:270-4. https://doi.org/10.1136/gut.52.2.270
  58. Eriksson JW. Metabolic stress in insulin's target cells leads to ROS accumulation - a hypothetical common pathway causing insulin resistance. FEBS Lett 2007;581:3734-42. https://doi.org/10.1016/j.febslet.2007.06.044
  59. Hennig R, Kekis PB, Friess H, Adrian TE, Buchler MW. Pancreatic polypeptide in pancreatitis. Peptides 2002;23:331-8. https://doi.org/10.1016/S0196-9781(01)00605-2