Skip to main content
SpringerLink
Log in

Mesna Alleviates Cerulein-Induced Acute Pancreatitis by Inhibiting the Inflammatory Response and Oxidative Stress in Experimental Rats

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

Acute pancreatitis (AP) is a sudden inflammation of the pancreas that may be life-threatening disease with high mortality rates, particularly in the presence of systemic inflammatory response and multiple organ failure. Oxidative stress has been shown to be involved in the pathophysiology of acute pancreatitis.

Aim

This study is designed to investigate the possible effect of mesna on an experimental model of cerulein-induced acute pancreatitis.

Methods

Animals were divided into five groups: Group 1 served as a control group given the saline; group II (mesna group) received mesna at a dose of (100 mg/kg per dose, i.p.) four times; group III (acute pancreatitis group) received cerulein at a dose of (20 µg/kg/dose, s.c.) four times with 1-h intervals; group VI, cerulein + mesna, was treated with mesna at a dose of (100 mg/kg, i.p.) 15 min before each cerulein injection.

Results

Animals with acute pancreatitis showed elevated serum amylase and lipase levels. Biochemical parameters showed increased pancreatic tumor necrosis factors-α (TNF-α) and interleukin-1β (IL-1β) levels. A disturbance in oxidative stress markers was evident by elevated pancreatic lipid peroxides (TBARS) and decline in pancreatic antioxidants’ concentrations including reduced glutathione (GSH); superoxide dismutase (SOD); and glutathione peroxidase (GSH-Px). Histological examination confirmed pancreatic injury. Pre-treatment with mesna was able to abolish the changes in pancreatic enzymes, oxidative stress markers (TBARS, SOD, GSH and GSH-Px), pancreatic inflammatory markers (TNF-α, IL-1β) as well as histological changes.

Conclusions

Mesna mitigates AP by alleviating pancreatic oxidative stress damage and inhibiting inflammation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Conti Bellocchi MC, Campagnola P, Frulloni L. Drug-induced acute pancreatitis. Pancreapedia Exocrine Pancreas Knowl Base. 2015;1:5. https://doi.org/10.3998/panc.2015.32.

    Article  Google Scholar 

  2. Almeida JL, Sampietre SN, Mendonça Coelho AM, et al. Statin pretreatment in experimental acute pancreatitis. JOP. 2008;9(4):431–439.

    PubMed  Google Scholar 

  3. Portelli M, Jones CD. Severe acute pancreatitis: pathogenesis, diagnosis and surgical management. Hepatobiliary Pancreat Dis Int. 2017;16(2):155–159.

    PubMed  Google Scholar 

  4. Majidi S, Golembioski A, Wilson SL, Thompson EC. Acute pancreatitis: etiology, pathology, diagnosis, and treatment. South Med J. 2017;110(11):727–732.

    CAS  PubMed  Google Scholar 

  5. Adiamah AE, Crook PM, Lobo DN. A systematic review of the epidemiology, pathophysiology and current management of hyperlipidaemic pancreatitis. Clin Nutr. 2018;37(6 Pt A):1810–1822.

    CAS  PubMed  Google Scholar 

  6. Forsmark CE, Vege SS, Wilcox CM. Acute pancreatitis. N Engl J Med. 2016;375(20):1972–1981.

    CAS  PubMed  Google Scholar 

  7. Leung PS, Chan YC. Role of oxidative stress in pancreatic inflammation. Antioxid Redox Signal. 2009;11(1):135–165.

    CAS  PubMed  Google Scholar 

  8. Dios ID. Inflammatory role of the acinar cells during acute pancreatitis. World J Gastrointest Pharmacol Ther. 2010;1(1):15–20.

    PubMed  PubMed Central  Google Scholar 

  9. Criddle DN. Reactive oxygen species, Ca (2+) stores and acute pancreatitis; a step closer to therapy? Cell Calcium. 2016;60(3):180–189.

    CAS  PubMed  Google Scholar 

  10. Armstrong JA, Cash N, Soares PM, Souza MH, Sutton R, Criddle DN. Oxidative stress in acute pancreatitis: lost in translation? Free Radic Res. 2013;47(11):917–933.

    CAS  PubMed  Google Scholar 

  11. Milnerowicz H, Bukowski R, Jablonowska M, Sciskalska M, Milnerowicz S. The antioxidant profiles, lysosomal and membrane enzymes activity in patients with acute pancreatitis. Mediators Inflamm. 2014;2014:376518.

    PubMed  PubMed Central  Google Scholar 

  12. Abu-Zidan FM, Bonham MJ, Windsor JA. Severity of acute pancreatitis: a multivariate analysis of oxidative stress markers and modified Glasgow criteria. Br J Surg. 2000;87(8):1019–1023.

    CAS  PubMed  Google Scholar 

  13. Norberg KJ, Nania S, Li X, et al. RCAN1 is a marker of oxidative stress, induced in acute pancreatitis. Pancreatology. 2018;18(7):734–741.

    CAS  PubMed  Google Scholar 

  14. Solakoglu TH, Koseoglu S, Isikoglu O, Erel Ersoy O. Association between antioxidants and mild acute pancreatitis. Arab J Gastroenterol. 2017;18(4):201–205.

    PubMed  Google Scholar 

  15. Kambhampati S, Park W, Habtezion A. Pharmacologic therapy for acute pancreatitis. World J Gastroenterol. 2014;20(45):16868–16880.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Esrefoglu M. Experimental and clinical evidence of antioxidant therapy in acute pancreatitis. World J Gastroenterol. 2012;18(39):5533–5541.

    PubMed  PubMed Central  Google Scholar 

  17. Carrasco C, Marchena AM, Holguin-Arevalo MS, et al. Anti-inflammatory effects of melatonin in a rat model of caerulein-induced acute pancreatitis. Cell Biochem Funct. 2013;31(7):585–590.

    CAS  PubMed  Google Scholar 

  18. Ozkan E, Akyuz C, Dulundu E, et al. Protective effects of lycopene on cerulein-induced experimental acute pancreatitis in rats. J Surg Res. 2012;176(1):232–238.

    CAS  PubMed  Google Scholar 

  19. Gressier B, Lebegue N, Brunet C, et al. Scavenging of reactive oxygen species by letosteine, a molecule with two blocked-SH groups Comparison with free-SH drugs. Pharm World Sci. 1995;17(3):76–80.

    CAS  PubMed  Google Scholar 

  20. Skinner N, Sharkey IM, Pearson ADJ, Craft AW. Ifosfamide, mesna and nephrotoxicity in children. J Clin Oncol. 1993;11:173–190.

    CAS  PubMed  Google Scholar 

  21. Triantafyllidis I, Poutahidis T, Taitzoglou I, Kesisoglou I, Lazaridis C, Botsios D. Treatment with Mesna and n-3 polyunsaturated fatty acids ameliorates experimental ulcerative colitis in rats. Int J Exp Pathol. 2015;96(6):433–443.

    CAS  PubMed  Google Scholar 

  22. Ypsilantis P, Tentes I, Lambropoulou M, et al. Prophylaxis with mesna prevents oxidative stress induced by ischemia reperfusion in the intestine via inhibition of nuclear factor-kappa B activation. J Gastroenterol Hepatol. 2008;23(2):328–335.

    CAS  PubMed  Google Scholar 

  23. Buyukberber M, Savas MC, Bagci C, et al. The beneficial effect of propolis on cerulein-induced experimental acute pancreatitis in rats. Turk J Gastroenterol. 2009;20(2):122–128.

    PubMed  Google Scholar 

  24. Ypsilantis P, Lambropoulou M, Tentes I, Kortsaris A, Papadopoulos N, Simopoulos C. Mesna protects intestinal mucosa from ischemia/reperfusion injury. J Surg Res. 2006;134(2):278–284.

    CAS  PubMed  Google Scholar 

  25. Buege JA, Aust SD. Microsomal lipid peroxidation methods. Enzymol. 1978;52:302–310.

    CAS  Google Scholar 

  26. Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959;82(1):70–77.

    CAS  Google Scholar 

  27. Nagi MN, Suneja SK, Cook L. Depletion of rat hepatic glutathione and inhibition of microsomal trans-2-Enoyl-CoA reductase activity following administration of Dec-2-ynol and Dec-2-ynoic acid. Arch Biochem Biophys. 1992;293:71–87.

    CAS  PubMed  Google Scholar 

  28. Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med. 1967;70(1):158–169.

    CAS  PubMed  Google Scholar 

  29. Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem. 1988;34(3):497–500.

    CAS  PubMed  Google Scholar 

  30. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72(1–2):248–254.

    CAS  Google Scholar 

  31. Tani S, Otsuki M, Itoh H, et al. Histologic and biochemical alterations in experimental acute pancreatitis induced by supramaximal cerulein stimulation. Int J Pancreatol. 1987;2:337–348.

    CAS  PubMed  Google Scholar 

  32. Dabrowski A, Gabryelewicz A, Wereszczynska-Siemiatkowska U, Chyczewski L. Oxygen-derived free radicals in cerulein-induced acute pancreatitis. Scand J Gastroenterol. 1988;23(10):1245–1249.

    CAS  PubMed  Google Scholar 

  33. Goerelick FS, Adler G, Kem HF. Cerulein induced pancreatitis. In: Go VLW, DiMagno EP, Gardner JP, Lebenthal E, Reber HA, Scheele GA, eds. The pancreas: biology, pathobiology, and disease. 2nd ed. New York: Raven Press; 1993:501–526.

    Google Scholar 

  34. Matull WR, Pereira SP, O’Donohue JW. Biochemical markers of acute pancreatitis. J Clin Pathol.. 2006;59(4):340–344.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Chvanov M, Petersen OH, Tepikin A. Free radicals and the pancreatic acinar cells: role in physiology and pathology. Philos Trans R Soc Lond B Biol Sci.. 2005;360(1464):2273–2284.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Curran FJM, Sattar N, Talwar D, Baxter JN, Imrie CW. Relationship of carotenoid and vitamins A and E with the acute inflammatory response in acute pancreatitis. Br J Surg. 2000;87(3):301–305.

    CAS  PubMed  Google Scholar 

  37. Amirshahrokhi K, Khalili AR. Gastroprotective effect of 2-mercaptoethane sulfonate against acute gastric mucosal damage induced by ethanol. Int Immunopharmacol. 2016;34:183–188.

    CAS  PubMed  Google Scholar 

  38. Sener G, Sehirli O, Ercan F, Sirvanci S, Gedik N, Kacmaz A. Protective effect of MESNA (2-mercaptoethane sulfonate) against hepatic ischemia/reperfusion injury in rats. Surg Today. 2005;35(7):575–580.

    CAS  PubMed  Google Scholar 

  39. Kabasakal L, Sehirli AO, Cetinel S, Cikler E, Gedik N, Sener G. Mesna (2-mercaptoethane sulfonate) prevents ischemia/reperfusion induced renal oxidative damage in rats. Life Sci. 2004;75(19):2329–2340.

    CAS  PubMed  Google Scholar 

  40. Bopanna S, Nayak B, Prakash S, Shalimar, Mahapatra SJ, Garg PK. Increased oxidative stress and deficient antioxidant levels may be involved in the pathogenesis of idiopathic recurrent acute pancreatitis. Pancreatology. 2017;17(4):529–533.

    CAS  PubMed  Google Scholar 

  41. Sener G, Sehirli O, Cetinel S, Yeğen BG, Gedik N, Ayanoğlu-Dülger G. Protective effects of MESNA (2-mercaptoethane sulphonate) against acetaminophen-induced hepatorenal oxidative damage in mice. J Appl Toxicol. 2005;25:20–29.

    CAS  PubMed  Google Scholar 

  42. Sener G, Kabasakal L, Sehirli O, Ercan F, Gedik N. 2-Mercaptoethane sulfonate (MESNA) protects against biliary obstruction-induced oxidative damage in rats. Hepatol Res. 2006;35(2):140–146.

    CAS  PubMed  Google Scholar 

  43. Al Maruf A, O’Brien PJ, Naserzadeh P, Fathian R, Salimi A, Pourahmad J. Methotrexate induced mitochondrial injury and cytochrome c release in rat liver hepatocytes. Drug Chem Toxicol. 2018;41(1):51–61.

    CAS  PubMed  Google Scholar 

  44. Pereda J, Sabater L, Aparisi L, et al. Interaction between cytokines and oxidative stress in acute pancreatitis. Curr Med Chem. 2006;13(23):2775–2787.

    CAS  PubMed  Google Scholar 

  45. Duan L, Ma Y, Chi J, Wang X, Wesley AJ, Chen X. The regulatory role of immunosuppressants on immune abnormalities in acute pancreatitis. Biomed Rep. 2014;2(2):193–198.

    CAS  PubMed  Google Scholar 

  46. Watanabe T, Kudo M, Strober W. Immunopathogenesis of pancreatitis. Mucosal Immunol. 2017;10(2):283–298.

    CAS  PubMed  Google Scholar 

  47. Gloire G, Legrand-Poels S, Piette J. NF-kappaB activation by reactive oxygen species: fifteen years later. Biochem Pharmacol. 2006;72(11):1493–1505.

    CAS  PubMed  Google Scholar 

  48. Jeelani R, Jahanbakhsh S, Kohan-Ghadr HR, et al. Mesna (2-mercaptoethane sodium sulfonate) functions as a regulator of myeloperoxidase. Free Radic Biol Med. 2017;110:54–62.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgment

The authors extend their appreciation to the Deanship of Scientific Research at King Saud University for funding this work through the Undergraduate Research Support Program, Project no. (URSP-17-48).

Author information

Authors and Affiliations

  1. Physiology and Pharmacology Department, College of Medicine and King Khalid University Hospital, King Saud University, P.O. Box 2925, Riyadh, 11461, Saudi Arabia

    Hanan H. Hagar

  2. Pharmacology and Toxicology Department, College of Pharmacy, Zagazig University, Zagazig, Egypt

    Hanan H. Hagar

  3. College of Medicine and King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia

    Sarah A. Almubrik & Sarah N. Aljasser

  4. College of Medicine, Zagazig University, Zagazig, Egypt

    Nada M. Attia

Authors
  1. Hanan H. Hagar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sarah A. Almubrik
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nada M. Attia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sarah N. Aljasser
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hanan H. Hagar.

Ethics declarations

Conflict of interest

All authors declare that they have 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

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hagar, H.H., Almubrik, S.A., Attia, N.M. et al. Mesna Alleviates Cerulein-Induced Acute Pancreatitis by Inhibiting the Inflammatory Response and Oxidative Stress in Experimental Rats. Dig Dis Sci 65, 3583–3591 (2020). https://doi.org/10.1007/s10620-020-06072-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-020-06072-1

Keywords

Search

Navigation