Digestive Diseases and Sciences

, Volume 63, Issue 6, pp 1497–1505 | Cite as

Anti-inflammatory and Antioxidant Effects of Captopril Compared to Methylprednisolone in l-Arginine-Induced Acute Pancreatitis

  • Nahla E. El-Ashmawy
  • Naglaa F. Khedr
  • Hoda A. El-Bahrawy
  • Omnia B. HamadaEmail author
Original Article



Acute pancreatitis (AP) is an inflammatory disease mediated by damage in acinar cells and pancreatic inflammation with infiltration of leukocytes. The pancreatic renin–angiotensin system may play an important role in the pathogenesis of AP.


The present study aimed to investigate the possible protective role of captopril (CAP), an angiotensin-converting enzyme inhibitor, in attenuating l-arginine-induced AP rat model and to elucidate the underlying molecular mechanisms.


Forty-eight adult male Wister rats were divided into four equal groups: control group (vehicle, orally for 10 days), AP group (3 g/kg l-arginine, single i.p.) on 10th day of the experiment, CAP group (50 mg/kg captopril, orally, once daily), and MP group (30 mg/kg methylprednisolone, orally, once daily). CAP and MP were administered for 10 days prior to l-arginine injection. Rats were sacrificed 24 h after arginine injection. Inflammatory biomarkers; tumor necrosis factor alpha (TNF-α) concentration, myeloperoxidase (MPO) activity, and inducible nitric oxide synthase (iNOS) gene expression were determined in pancreas. Oxidative stress biomarkers; pancreatic nitric oxide (NO) and reduced glutathione (GSH) concentrations were measured. Moreover, serum α-amylase and lipase activities were measured and histopathological studies of the pancreas were done.


CAP group showed a significant reduction in pancreatic TNF-α concentration, MPO activity, NO concentration, and downregulation of iNOS gene expression compared to AP group. CAP group also showed a significant increase in GSH concentration with amelioration of histological changes of AP as well as MP group.


Captopril treatment showed a protective and comparable effect with MP treatment in AP rat model.


Acute pancreatitis Captopril iNOS Myeloperoxidase TNF-α 



The authors gratefully acknowledge Dr. Mohammed Fawzy for his help in conducting and interpreting the histopathological investigations.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Gaddam RR, Ang AD, Badiei A, Chambers ST, Bhatia M. Alteration of the renin-angiotensin system in caerulein-induced acute pancreatitis in the mouse. Pancreatology. 2015;15:647–653.CrossRefPubMedGoogle Scholar
  2. 2.
    Chan YC, Leung PS. The renin-angiotensin system and reactive oxygen species: implications in pancreatitis. Antioxid Redox Signal. 2011;15:2743–2755.CrossRefPubMedGoogle Scholar
  3. 3.
    Leung PS. The physiology of a local renin-angiotensin system in the pancreas. J Physiol. 2007;580:31–37.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Pan Z, Feng L, Long H, Wang H, Feng J, Chen F. Effects of local pancreatic renin-angiotensin system on the microcirculation of rat with severe acute pancreatitis. Korean J Physiol Pharmacol. 2015;19:299–307.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Skipworth J, Szabadkai G, Olde Damink S, Leung P, Humphries S, Montgomery H. Pancreatic renin-angiotensin systems in health and disease. Aliment Pharmacol Ther. 2011;34:840–852.CrossRefPubMedGoogle Scholar
  6. 6.
    Ip SP, Kwan PC, Williams CH, Pang S, Hooper NM, Leung PS. Changes of angiotensin-converting enzyme activity in the pancreas of chronic hypoxia and acute pancreatitis. Int J Biochem Cell Biol. 2003;35:944–954.CrossRefPubMedGoogle Scholar
  7. 7.
    Manohar M, Verma AK, Venkateshaiah SU, Sanders NL, Mishra A. Pathogenic mechanisms of pancreatitis. World J Gastrointest Pharmacol Ther. 2017;8:10–25.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Pérez S, Pereda J, Sabater L, Sastre J. Redox signaling in acute pancreatitis. Redox Biol. 2015;5:1–14.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Abdel-Gawad SK. Therapeutic and protective effect of wheat germ oil on l-arginine-induced acute pancreatitis in adult Albino rats. J Cell Sci Ther. 2015;S8:S8-004. Scholar
  10. 10.
    Dong LH, Liu ZM, Wang SJ, et al. Corticosteroid therapy for severe acute pancreatitis: a meta-analysis of randomized, controlled trials. Int J Clin Exp Pathol. 2015;8:7654–7660.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Becker DE. Basic and clinical pharmacology of glucocorticosteroids. Anesth Prog. 2013;60:25–32.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Mikrut K, Kupsz J, Koźlik J, Krauss H, Pruszyńska-Oszmałek E, Gibas-Dorna M. Angiotensin-converting enzyme inhibitors reduce oxidative stress intensity in hyperglicemic conditions in rats independently from bradykinin receptor inhibitors. Croat Med J. 2016;57:371–380.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Sağlam E, Şehirli AÖ, Özdamar EN, et al. Captopril protects against burn-induced cardiopulmonary injury in rats. Ulus Travma Acil Cerrahi Derg. 2014;20:151–160.CrossRefPubMedGoogle Scholar
  14. 14.
    Jeandidier N, Klewansky M, Plnget M. Captopril-induced acute pancreatitis. Diabetes Care. 1995;18:410–411.CrossRefPubMedGoogle Scholar
  15. 15.
    Oruc N, Ozutemiz O, Nart D, Yuce G, Celik HA, Ilter T. Inhibition of renin-angiotensin system in experimental acute pancreatitis in rats: a new therapeutic target? Exp Toxicol Pathol. 2010;62:353–360.CrossRefPubMedGoogle Scholar
  16. 16.
    Yu Q-H, Guo J-F, Chen Y, Guo X-R, Du Y-Q, Li Z-S. Captopril pretreatment protects the lung against severe acute pancreatitis induced injury via inhibiting angiotensin II production and suppressing Rho/ROCK pathway. Kaohsiung J Med Sci. 2016;32:439–445.CrossRefPubMedGoogle Scholar
  17. 17.
    Hasan MI, Bakr AG, Shalkami A-GS. Modulation of l-arginine-induced acute pancreatitis by meloxicam and/or L-carnitine in rats. IJBCP. 2015;4:1247–1253.Google Scholar
  18. 18.
    Dawra R, Saluja AK. l-arginine-induced experimental acute pancreatitis. Pancreapedia Exocrine Pancreas Knowl Base. 2012. Scholar
  19. 19.
    Biradar S, Veeresh B. Protective effect of lawsone on l-Arginine induced acute pancreatitis in rats. Indian J Exp Biol. 2013;51:256–261.PubMedGoogle Scholar
  20. 20.
    Melo CM, Carvalho KM, Neves JC, et al. Alpha, beta-amyrin, a natural triterpenoid ameliorates l-arginine-induced acute pancreatitis in rats. World J Gastroenterol. 2010;16:4272–4280.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Winn-Deen ES, David H, Sigler G, Chavez R. Development of a direct assay for alpha-amylase. Clin Chem. 1988;34:2005–2008.PubMedGoogle Scholar
  22. 22.
    Panteghini M, Bonora R, Pagani F. Measurement of pancreatic lipase activity in serum by a kinetic colorimetric assay using a new chromogenic substrate. Ann Clin Biochem. 2001;38:365–370.CrossRefPubMedGoogle Scholar
  23. 23.
    Corti A, Fassina G, Marcucci F, Barbanti E, Cassani G. Oligomeric tumor necrosis factor α slowly converts into inactive forms at bioactive levels. Biochem J. 1992;284:905–910.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193:265–275.PubMedGoogle Scholar
  25. 25.
    Bradley PP, Priebat DA, Christensen RD, Rothstein G. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Investig Dermatol. 1982;78:206–209.CrossRefPubMedGoogle Scholar
  26. 26.
    Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959;82:70–77.CrossRefPubMedGoogle Scholar
  27. 27.
    Miranda KM, Espey MG, Wink DA. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide. 2001;5:62–71.CrossRefPubMedGoogle Scholar
  28. 28.
    Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative CT method. Nat Protoc. 2008;3:1101.CrossRefPubMedGoogle Scholar
  29. 29.
    Schmidt J, Lewandrowski K, Fernandez-del Castillo C, et al. Histopathologic correlates of serum amylase activity in acute experimental pancreatitis. Dig Dis Sci. 1992;37:1426–1433.CrossRefPubMedGoogle Scholar
  30. 30.
    Field A. Discovering statistics using SPSS. London: Sage Publications; 2009.Google Scholar
  31. 31.
    Camargo E, Santana D, Silva C, et al. Inhibition of inducible nitric oxide synthase-derived nitric oxide as a therapeutical target for acute pancreatitis induced by secretory phospholipase A2. Eur J Pain. 2014;18:691–700.CrossRefPubMedGoogle Scholar
  32. 32.
    Soliman ME-S, Kefafy MA, Mansour MA, Ali AF, Esa WAII. 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;27:801–808.CrossRefGoogle Scholar
  33. 33.
    Biradar S. Naturally occurring active constituent can be one of the choice to treat acute pancreatitis. WJPPS. 2013;2:3878–3888.Google Scholar
  34. 34.
    Meher S, Mishra TS, Sasmal PK, et al. Role of biomarkers in diagnosis and prognostic evaluation of acute pancreatitis. J Biomark. 2015. Scholar
  35. 35.
    Kaur J, Sidhu S, Chopra K, Khan M. Protective effect of Mimosa pudica L in an l-arginine model of acute necrotising pancreatitis in rats. J Nat Med. 2016;70:423–434.CrossRefPubMedGoogle Scholar
  36. 36.
    Kui B, Balla Z, Végh ET, et al. Recent advances in the investigation of pancreatic inflammation induced by large doses of basic amino acids in rodents. Lab Investig. 2014;94:138–149.CrossRefPubMedGoogle Scholar
  37. 37.
    Gad AM, Fawzy HM, El-Raouf OMA, El-Sayeh BM, Abdallah DM. Antiapoptotic effect of captopril in cisplatin-induced kidney injury in rats. Egypt J Hosp Med. 2016;65:573–582.CrossRefGoogle Scholar
  38. 38.
    Vinod P. Pathophysiology of diabetic nephropathy. Clin Queries Nephrol. 2012;1:121–126.CrossRefGoogle Scholar
  39. 39.
    Araujo LFL, Holand ARR, Paludo AdO, et al. Effect of the systemic administration of methylprednisolone on the lungs of brain-dead donor rats undergoing pulmonary transplantation. Clinics. 2014;69:128–133.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Meng H, Liu Y, Li K, Li J. Comparison of the effects of methotrexate and methylprednisolone in spinal cord injury in rats. Drug Res. 2015;65:437–441.Google Scholar
  41. 41.
    Eid AH, Abdelkader NF, El-Raouf OMA, Fawzy HM, El-Denshary E-E-DS. Captopril and telmisartan ameliorate cisplatin-induced testicular damage in rats via anti-inflammatory and antioxidant pathways. IJSRP. 2016;6:408–420.Google Scholar
  42. 42.
    Moghadam Jafari A, Koohi MK, Ghazi-Khansari M, Pasalar P. Protective effects of captopril against aflatoxin b1-induced hepatotoxicity in isolated perfused rat liver. Zahedan J Res Med Sci. 2014;16:29–32.Google Scholar
  43. 43.
    Fouad AA, Jresat I. Captopril and telmisartan treatments attenuate cadmium-induced testicular toxicity in rats. Fundam Clin Pharmacol. 2013;27:152–160.CrossRefPubMedGoogle Scholar
  44. 44.
    Ko Y-H, Tsai M-S, Lee P-H, Liang J-T, Chang K-C. Methylprednisolone stiffens aortas in lipopolysaccharide-induced chronic inflammation in rats. PloS ONE. 2013;8:e69636.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Nahla E. El-Ashmawy
    • 1
  • Naglaa F. Khedr
    • 1
  • Hoda A. El-Bahrawy
    • 1
  • Omnia B. Hamada
    • 1
    Email author
  1. 1.Department of Biochemistry, Faculty of PharmacyTanta UniversityTantaEgypt

Personalised recommendations