The protective role of melatonin on L-arginine-induced acute pancreatitis in adult male albino rats

• Autorzy: Sadek A.S. , Khattab R.T.
• Języki publikacji: EN

Abstrakty

EN

Background: Acute pancreatitis (AP) is an inflammatory disease that has an increasing incidence worldwide. AP is associated with high morbidity and mortality rates ranging 15–40% in its severe form. Oxidative stress plays an important role in pancreatic acinar cell injury in case of AP. Melatonin (Mel) is proven to have both antioxidant and anti-inflammatory effects. The aim of the work was to investigate the protective role of Mel against L-arginine (L-arg)-induced AP in adult male albino rats. Materials and methods: Thirty-six adult male albino rats were used in this study. Animals were divided into four groups; Control group (Group A; n = 6), Mel group (Group B; n = 6), L-arg group (Group C; n = 12) receiving two doses of L-arg injection with 1 h interval in-between, and L-arg+Mel group (Group D; n = 12) receiving Mel 1 h after each L-arg injection. 24 h after the second L-arg injection, the serum levels of amylase (AM), lipase (LP), interleukin-6 (IL-6) and tumour necrotic factor-alpha (TNF-α) were determined. Then, pancreatic specimens were processed for histological and immunohistochemical staining with vascular endothelial growth factor (VEGF) and the area percentage of VEGF and collagen content were measured by digital image analysis. Results: Microscopic examination revealed that animals received L-arg only (Group C) showed loss of the pancreatic lobular architecture with marked fibrosis, acinar degeneration, inflammatory reaction and marked oedema with vascular congestion. Also, L-arg-induced AP caused a significant elevation of the serum levels of AM, LP, IL-6. All these histo-pathological and serological parameters were markedly improved by Mel administration. Conclusions: Melatonin exhibits strong therapeutic effects in the course of AP. Hence, the use of Mel as adjuvant treatment in AP is recommended. (Folia Morphol 2017; 76, 1: 66–73)

• Wydawca: -
• Czasopismo: Folia Morphologica
• Rocznik: 2017
• Tom: 76
• Numer: 1
• Opis fizyczny: p.66-72,fig.

Twórcy

autor

Sadek A.S.

• Department of Anatomy, Taibah University, Al-Madinah Al-Munawarah, Kingdom of Saudi Arabia, Saudi Arabia
• Anatomy and Embryology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt

autor

Khattab R.T.

• Department of Anatomy, Taibah University, Al-Madinah Al-Munawarah, Kingdom of Saudi Arabia, Saudi Arabia
• Anatomy and Embryology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt

Bibliografia

• 1. Akyuz C, Sehirli AO, Topaloglu U, et al. Protective Effects of Proanthocyanidin on Cerulein-induced Acute Pancreatic Inflammation in Rats. Gastroenterology Res. 2009; 2(1): 20–28, doi: 10.4021/gr2009.02.1276, indexed in Pubmed: 27956946.
• 2. Alhan E, Kalyoncu NI, Kural BV, et al. Effects of melatonin on acute necrotizing pancreatitis in rats. Z Gastroenterol. 2004; 42(9): 967–972, doi: 10.1055/s-2004-813321, indexed in Pubmed: 15455265.
• 3. Allegra M, Reiter RJ, Tan DX, et al. The chemistry of melatonin’s interaction with reactive species. J Pineal Res. 2003; 34(1): 1–10, doi: 10.1034/j.1600-079x.2003.02112.x, indexed in Pubmed: 12485365.
• 4. Apte MV, Wilson JS. Mechanisms of pancreatic fibrosis. Dig Dis. 2004; 22(3): 273–279, doi: 10.1159/000082799, indexed in Pubmed: 15753610.
• 5. Arana V, Paz Y, González A, et al. Healing of diabetic foot ulcers in L-arginine-treated patients. Biomed Pharmacother. 2004; 58(10): 588–597, doi: 10.1016/j.biopha.2004.09.009, indexed in Pubmed: 15589068.
• 6. Aysel K, Mehmet I, Şeval A, et al. Serum TNF-alpha levels in acute and chronic pancreatitis. Eur J Gen Med. 2009; 6: 103–107.
• 7. Bancroft JB, Gamble M. Theory and practice of histological techniques, 5th Ed. Churchill Livingstone. Edinburgh, 2002.
• 8. Belyaev O, Herzog T, Munding J, et al. Protective role of endogenous melatonin in the early course of human acute pancreatitis. J Pineal Res. 2011; 50(1): 71–77, doi: 10.1111/j.1600-079X.2010.00811.x, indexed in Pubmed: 20964708.
• 9. Biczó G, Hegyi P, Berczi S, et al. Inhibition of arginase activity ameliorates L-arginine-induced acute pancreatitis in rats. Pancreas. 2010; 39(6): 868–874, doi: 10.1097/MPA.0b013e3181d371f8, indexed in Pubmed: 20697209.
• 10. Boujendar S, Arany E, Hill D, et al. Taurine supplementation of a low protein diet fed to rat dams normalizes the vascularization of the fetal endocrine pancreas. J Nutr. 2003; 133(9): 2820–2825, doi: 10.1159/000243170, indexed in Pubmed: 12949371.
• 11. Braganza JM. Experimental acute pancreatitis. Curr Opin Gastroenterol. 1990; 6(5): 763–768, doi: 10.1097/00001574-199010000-00017.
• 12. Bruno MJ. Current insights into the pathogenesis of acute and chronic pancreatitis. Scand J Gastroenterol Suppl. 2001(234): 103–108, doi: 10.1080/003655201753265532, indexed in Pubmed: 11768555.
• 13. Bülbüller N, Doğru O, Umaç H, et al. [The effects of melatonin and pentoxiphylline on L-arginine induced acute pancreatitis]. Ulus Travma Acil Cerrahi Derg. 2005; 11(2): 108–114, indexed in Pubmed: 15877240.
• 14. Chen X, Sans MD, Strahler JR, et al. Quantitative organellar proteomics analysis of rough endoplasmic reticulum from normal and acute pancreatitis rat pancreas. J Proteome Res. 2010; 9(2): 885–896, doi: 10.1021/pr900784c, indexed in Pubmed: 19954227.
• 15. Chuang JI, Mohan N, Meltz ML, et al. Effect of melatonin on NF-kappa-B DNA-binding activity in the rat spleen. Cell Biol Int. 1996; 20(10): 687–692, doi: 10.1006/cbir.1996.0091, indexed in Pubmed: 8969462.
• 16. Czako L, Takacs T, Varga IS, et al. Involvement of oxygen-free radicals in L-arginine-induced acute pancreatitis. Dig Dis and Sci, 1998; 43(8): 432–434.
• 17. Delaney CP, McGeeney KF, Dervan P, et al. Pancreatic atrophy: a new model using serial intra-peritoneal injections of L-arginine. Scand J Gastroenterol. 1993; 28(12): 1086–1090, doi: 10.3109/00365529309098314, indexed in Pubmed: 8303212.
• 18. Drury R, Wallington E. Carleton Histological techniques, 5th Ed. Oxford University Press, London, New York and Toronto, 1980.
• 19. Esa WI, Soliman Ms, Kefafy M, et al. Histological study on the possible protective effect of pentoxifylline on pancreatic acini of l-arginine-induced acute pancreatitis in adult male albino rats. Menoufia Med J. 2014; 27(4): 801–808, doi: 10.4103/1110-2098.149789.
• 20. Esteban S, Garau C, Aparicio S, et al. Chronic melatonin treatment and its precursor L-tryptophan improve the monoaminergic neurotransmission and related behavior in the aged rat brain. J Pineal Res. 2010; 48(2): 170–177, doi: 10.1111/j.1600-079X.2009.00741.x, indexed in Pubmed: 20082664.
• 21. Hardman J, Shields C, Schofield D, et al. Intravenous antioxidant modulation of end-organ damage in L-arginineinduced experimental acute pancreatitis. Pancreatology. 2005; 5(4-5): 380–386, doi: 10.1159/000086538, indexed in Pubmed: 15980666.
• 22. Hegyi P, Rakonczay Z, Sári R, et al. L-arginine-induced experimental pancreatitis. World J. Gastroenterol. 2004; 10(14): 2003–2009, doi: 10.3748/wjg.v10.i14.2003, indexed in Pubmed: 15237423.
• 23. Jaworek J, Zwirska-Korczala K, Szklarczyk J, et al. Pinealectomy aggravates acute pancreatitis in the rat. Pharmacol Rep. 2010; 62(5): 864–873, doi: 10.1016/s1734-1140(10)70346-7, indexed in Pubmed: 21098869.
• 24. Kudari A, Wig JD, Vaiphei K, et al. Histopathological sequential changes in sodium taurocholate-induced acute pancreatitis. JOP. 2007; 8(5): 564–572, indexed in Pubmed: 17873460.
• 25. Kumar V, Abbas A, Fausto N. Robbins and Cotran pathologic basis of diseases, seventh edition. Elsevier Saunders, China, 2005; pp. 797–876.
• 26. Lechin F, van der Dijs B. Arginine-induced pancreatitis: involvement of the autonomic nervous system? Am J Physiol Gastrointest Liver Physiol. 2008; 294(6): G1450–G1451, doi: 10.1152/ajpgi.00327.2007, indexed in Pubmed: 18541710.
• 27. Li S, Chen Xi, Wu T, et al. Role of heparin on serum VEGF levels and local VEGF contents in reducing the severity of experimental severe acute pancreatitis in rats. Scand J Gastroenterol. 2012; 47(2): 237–244, doi: 10.3109/00365521.2011.647063, indexed in Pubmed: 22214372.
• 28. Melo CM, Carvalho KM, Neves JC, et al. Alpha,beta-amyrin, a natural triterpenoid ameliorates L-arginne-induced acute pancreatitis in rats, World J Gastroenterol, 2010; 16(34): 4272–4280.
• 29. Nandy D, Mukhopadhyay D. Growth factor mediated signaling in pancreatic pathogenesis. Cancers (Basel). 2011; 3(1): 841–871, doi: 10.3390/cancers3010841, indexed in Pubmed: 24212642.
• 30. Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z. Vascular endothelial growth factor (VEGF) and its receptors. FASEB J, 1999; 13: 9–22.
• 31. Nevalainen TJ, Aho HJ. Standards of morphological evaluation and histological grading in experimental acute pancreatitis. Eur Surg Res. 1992; 24 Suppl 1: 14–23, doi: 10.1159/000129235, indexed in Pubmed: 1601020.
• 32. Öberg-Welsh C, Sandler S, Andersson A, et al. Effects of vascular endothelial growth factor on pancreatic duct cell replication and the insulin production of fetal islet-like cell clusters in vitro. Mol Cell Endocrinol. 1997; 126(2): 125–132, doi: 10.1016/s0303-7207(96)03977-9.
• 33. Pérez S, Pereda J, Sabater L, et al. Redox signaling in acute pancreatitis. Redox Biol. 2015; 5: 1–14, doi: 10.1016/j.redox.2015.01.014, indexed in Pubmed: 25778551.
• 34. Pooran N, Indaram A, Singh P, et al. Cytokines (IL-6, IL-8, TNF): early and reliable predictors of severe acute pancreatitis. J Clin Gastroenterol. 2003; 37(3): 263–266, doi: 10.1097/00004836-200309000-00013, indexed in Pubmed: 12960727.
• 35. Qi W, Tan DX, Reiter RJ, et al. Melatonin reduces lipid peroxidation and tissue edema in cerulein-induced acute pancreatitis in rats. Dig Dis Sci. 1999; 44(11): 2257–2262, indexed in Pubmed: 10573371.
• 36. Robbins K. Basic pathology. Elsevier publications, Chicago, USA. 2002; pp. 675.
• 37. Saka M, Tüzün A, Ateş Y, et al. Acute pancreatitis possibly due to arginine use: a case report. Turk J Gastroenterol. 2004; 15(1): 56–58, indexed in Pubmed: 15264124.
• 38. Sidhu S, Pandhi P, Malhotra S, et al. Melatonin treatment is beneficial in pancreatic repair process after experimental acute pancreatitis. Eur J Pharmacol. 2010; 628(1-3): 282–289, doi: 10.1016/j.ejphar.2009.11.058, indexed in Pubmed: 19958759.
• 39. Silva Sd, Ximenes VF, Livramento JA, et al. High concentrations of the melatonin metabolite, N1-acetyl-N2-formyl5-methoxykynuramine, in cerebrospinal fluid of patients with meningitis: a possible immunomodulatory mechanism. J Pineal Res. 2005; 39(3): 302–306, doi: 10.1111/j.1600-079X.2005.00247.x, indexed in Pubmed: 16150112.
• 40. Smotkin J, Tenner S. Laboratory diagnostic tests in acute pancreatitis. J. Clin. Gastroenterol. 2002; 34(4): 459–462, doi: 10.1097/00004836-200204000-00018, indexed in Pubmed: 11907364.
• 41. Stebelová K, Herichová I, Zeman M. Diabetes induces changes in melatonin concentrations in peripheral tissues of rat. Neuro Endocrinol Lett. 2007; 28(2): 159–165, indexed in Pubmed: 17435669.
• 42. Szabolcs A, Reiter RJ, Letoha T, et al. Effect of melatonin on the severity of L-arginine-induced experimental acute pancreatitis in rats. World J Gastroenterol. 2006; 12(2): 251–258, doi: 10.3748/wjg.v12.i2.251, indexed in Pubmed: 16482626.
• 43. Takács T, Czakó L, Morschl E, et al. The role of nitric oxide in edema formation in L-arginine-induced acute pancreatitis. Pancreas. 2002; 25(3): 277–282, doi: 10.1097/00006676-200210000-00010, indexed in Pubmed: 12370539.
• 44. Tashiro M, Schäfer C, Yao H, et al. Arginine induced acute pancreatitis alters the actin cytoskeleton and increases heat shock protein expression in rat pancreatic acinar cells. Gut. 2001; 49(2): 241–250, doi: 10.1136/gut.49.2.241, indexed in Pubmed: 11454802.
• 45. Zhang Z, Wang Y, Dong M, et al. Oxymatrine ameliorates L-arginine-induced acute pancreatitis in rats. Inflammation. 2012; 35(2): 605–613, doi: 10.1007/s10753-011-9352-2, indexed in Pubmed: 21633783.

Identyfikatory

DOI

10.5603/FM.a2016.0029