Skip to main content
Log in

Effects of Clotrimazol on the Acute Necrotizing Pancreatitis in Rats

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

This study aims to investigate the influence of clotrimazol (CLTZ) on acute necrotizing pancreatitis (ANP) induced by glycodeoxycholic acid in rats. Rats were divided into five groups as sham + saline, sham + CLTZ, sham + polyethylene glycol, ANP + saline, and ANP + CLTZ. ANP in rats was induced by glycodeoxycholic acid. The extent of acinar cell injury, mortality, systemic cardiorespiratory variables, functional capillary density (FCD), renal/hepatic functions, and changes in some enzyme markers for pancreatic and lung tissue were investigated during ANP in rats. The use of CLTZ after the induction of ANP resulted in a significant decrease in the mortality rate, pancreatic necrosis, and serum activity of amylase, alanine aminotransferase, interleukin-6, lactate dehydrogenase in bronchoalveolar lavage fluid, serum concentration of urea, and tissue activity of myeloperoxidase, and malondialdehyde in the pancreas and lung and a significant increase in concentrations of calcium, blood pressure, urine output, pO2, and FCD. This study showed that CLTZ demonstrated beneficial effect on the course of ANP in rats. Therefore, it may be used in the treatment of acute pancreatitis.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

REFERENCES

  1. Schwarz, M., J. Thomson, H. Meyer, M.W. Büchler, and H.G. Beger. 2000. Frequency and time course of pancreatic and extra pancreatic bacterial infection in experimental pancreatitis in rats. Surgery 127: 427–432.

    Article  PubMed  CAS  Google Scholar 

  2. Saluja, A.K., and M.L. Steer. 1999. Pathophysiology of pancreatitis. Role of cytokines and inflammatory mediators. Digestion 60: 27–33.

    Article  PubMed  CAS  Google Scholar 

  3. Klar, E., K. Messmer, A.L. Warshaw, and C. Herfarth. 1990. Pancreatic ischemia in experimental acute pancreatitis: mechanism, significance and therapy. British Journal of Surgery 77: 1205–1210.

    Article  PubMed  CAS  Google Scholar 

  4. Alhan, E., U. Kücüktülü, C. Ercin, O. Deger, and R. Cicek. 2001. The effects of dopexamine on acute necrotizing pancreatitis in rats. The European Journal of Surgery 167: 761–766.

    Article  PubMed  CAS  Google Scholar 

  5. Norman, J. 1998. The role of cytokines in the pathogenesis of acute pancreatitis. American Journal of Surgery 1175: 76–83.

    Article  Google Scholar 

  6. Alhan, E., N.I. Kalyoncu, B. Vanizor, and C. Erçin. 2004. Effects of melatonin on acute pancreatitis in rats. Zeitschrift für Gastroenterologie 42: 967–972.

    Article  PubMed  CAS  Google Scholar 

  7. Hg, B., R. Bittner, and M. Büchler. 1986. Hemodynamic data pattern in patients with acute pancreatitis. Gastroenterology 90: 74–79.

    Google Scholar 

  8. Rau, B., B. Poch, F. Gansauge, A. Bauer, K.A. Nüssler, T. Nevalainen, M.H. Schoenberg, and H.G. Beger. 2000. Pathophysiologic role of oxygen free radicals in acute pancreatitis. Annals of Surgery 31: 352–360.

    Article  Google Scholar 

  9. Yamamoto, Y. 1985. Oxidation of biological membranes and its inhibition. Free radical chain oxidation of erythrocyte ghost membranes by oxygen. Biochimica et Biophysica Acta 819: 29–36.

    Article  PubMed  CAS  Google Scholar 

  10. Faiber, J.L., M.E. Kyle, and J.B. Coleman. 1990. Mechanisms of cell injury by activated oxygen species. Laboratory Investigation 62: 670–679.

    Google Scholar 

  11. Hotter, G., D. Closa, N. Prats, F. Pi, E. Gelpi, and J. Rosello-Catafau. 1997. Free radical enhancement promotes leukocytes recruitment through a PAF and LTB4 dependent mechanism. Free Radical Biology & Medicine 22: 947–954.

    Article  CAS  Google Scholar 

  12. Stanfey, H., G.B. Bulkley, and J.L. Cameron. 1984. The role of oxygen-derived free radicals in the pathogenesis of acute pancreatitis. Annals of Surgery 200: 405–413.

    Article  Google Scholar 

  13. Schulz, H.U., and C. Niederau. 1994. Oxidative stress-induced changes in pancreatic acinar cells: Insight from in vitro studies. Hepato-Gastroenterology 41: 309–312.

    PubMed  CAS  Google Scholar 

  14. Schoenberg, M.H., D. Birk, and H.G. Beger. 1995. Oxidative stress in acute and chronic pancreatitis. The American Journal of Clinical Nutrition 62: 1306S–1314S.

    PubMed  CAS  Google Scholar 

  15. Osmanağaoğlu, M.A., M. Kesim, E. Yulug, A. Menteşe, and C. Karahan. 2012. Ovarian-protective effects of clotrimazole on ovarian ischemia/reperfusion Injury in a rat ovarian-torsion model. Gynecologic and Obstetric Investigation 74: 125–130.

    Article  PubMed  Google Scholar 

  16. Vanden Bossche, H., P. Marichal, J. Gorrens, M.C. Coene, G. Willemsens, D. Bellens, I. Roels, H. Moereels, and P.A. Janssen. 1989. Biochemical approaches to selective antifungal activity. Focus on azole antifungals. Mycoses 32: 35–52.

    Article  PubMed  CAS  Google Scholar 

  17. Alvarez, J., M. Montero, and J. Garcia-Sancho. 1992. High affinity inhibition of Ca2+-dependent K+ channels by cytochrome P450 inhibitors. The Journal of Biological Chemistry 267: 11789–11793.

    PubMed  CAS  Google Scholar 

  18. Isaev, N.K., E.V. Stelmashook, U. Dirnagl, N.A. Andreeva, L. Manuhova, V.S. Vorobjev, I.N. Sharonova, V.G. Skrebitsky, I.V. Victorov, J. Katchanov, M. Weih, and D.B. Zorov. 2002. Neuroprotective effects of the antifungal drug clotrimazole. Neuroscience 113: 47–53.

    Article  PubMed  CAS  Google Scholar 

  19. Schmidt, J., M.D. Rattner, and K. Lewandrowski. 1992. A better model of acute pancreatitis for evaluating therapy. Annals of Surgery 215: 44–56.

    Article  PubMed  CAS  Google Scholar 

  20. Dobschuetz, E., P. Biberthaler, T. Mussack, S. Langer, K. Messmer, and T. Hoffmann. 2003. Noninvasive in vivo assessment of the pancreatic microcirculation: Orthogonal polarization spectral imaging. Pancreas 26: 139–143.

    Article  Google Scholar 

  21. Sookhal, S., J.J. Wang, M. McCourt, W. Kwan, D.H. Bouchier, and P. Redmond. 2002. A novel therapeutic strategy for attenuating neutrophil-mediated lung injury in vivo. Annals of Surgery 235: 283–291.

    Google Scholar 

  22. Lankisch, P.G., U. Pohl, J. Otto, and G. Rahlf. 1988. When should treatment of acute experimental pancreatitis be started? The early phase of bile-induced acute pancreatitis. Research in Experimental Medicine 188: 123–129.

    Article  PubMed  CAS  Google Scholar 

  23. Schierwagen, C., A.C. Bylund-Fellenius, and C. Lundberg. 1990. Improved method for quantification of tissue PMN accumulation measured by myeloperoxidase activity. Journal of Pharmacological Methods 23: 179–186.

    Article  PubMed  CAS  Google Scholar 

  24. Buege, J.A., and S.D. Aust. 1978. Microsomal lipid peroxidation. Methods in Enzymology 52: 302–310.

    Article  PubMed  CAS  Google Scholar 

  25. Lowry, O.H., N.J. Rosebrough, A.L. Farr, and R.J. Randall. 1951. Protein measurement with the Folin phenol reagent. The Journal of Biological Chemistry 193: 265–275.

    PubMed  CAS  Google Scholar 

  26. Jensen, B.S., M. Hertz, P. Christophersen, and L.S. Madsen. 2002. The Ca2+-activated K+ channel of intermediate conductance: A possible target for immune suppression. Expert Opinion on Therapeutic Targets 6: 623–636.

    Article  PubMed  CAS  Google Scholar 

  27. Lang, F., C. Birka, S. Myssina, K.S. Lang, P.A. Lang, V. Tanneur, C. Duranton, T. Wieder, and S.M. Huber. 2004. Erythrocyte ion channels in regulation of apoptosis. Advances in Experimental Medicine and Biology 559: 211–217.

    Article  PubMed  CAS  Google Scholar 

  28. Miller, B.A. 2006. The role of TRP channels in oxidative stress-induced cell death. The Journal of Membrane Biology 209: 31–41.

    Article  PubMed  CAS  Google Scholar 

  29. Usul, H., E. Arslan, T. Cansever, et al. 2008. Effects of clotrimazole on experimental spinal cord ischemia/reperfusion injury in rats. Spine 33: 2863.

    Article  PubMed  Google Scholar 

  30. Chou, C.C., C.A. Lunn, and N.J. Murgolo. 2008. KCa3.1: target and marker for cancer, autoimmune disorder and vascular inflammation? Expert Review of Molecular Diagnostics 8: 179–187.

    Article  PubMed  CAS  Google Scholar 

  31. Thapa, D., J.S. Lee, S.Y. Park, et al. 2008. Clotrimazole ameliorates intestinal inflammation and abnormal angiogenesis by inhibiting interleukin-8 expression through a nuclear factor-Kβ-dependent manner. The Journal of Pharmacology and Experimental Therapeutics 327: 353–364.

    Article  PubMed  CAS  Google Scholar 

  32. Bowles, D.K. 2009. The intermediate-conductance Ca2+-activated K+ channel (KCa3.1) in vascular disease. Cardiovascular & Hematological Agents in Medicinal Chemistry 7: 1–11.

    Article  Google Scholar 

  33. Marcondes, M.C., M. Sola-Penna, and P. Zancan. 2010. Clotrimazole potentiates the inhibitory effects of ATP on the key glycolytic enzyme 6-phosphofructo-1-kinase. Archives of Biochemistry and Biophysics 497: 62–67.

    Article  PubMed  CAS  Google Scholar 

  34. Iannelli, A., G. de Sousa, N. Zucchini, M.C. Saint-Paul, J. Gugenheim, and R. Rahmani. 2011. Anti-apoptotic pro-survival effect of clotrimazole in a normothermic ischemia reperfusion injury animal model. The Journal of Surgical Research 171: 101–107.

    Article  PubMed  CAS  Google Scholar 

  35. Horng, C.T., N.N. Chiang, I.L. Chen, W.Z. Liang, I.S. Chen, D.H. Kuo, P.C. Shieh, and C.R. Jan. 2013. Effect of clotrimazole on cytosolic Ca(2+) rise and viability in HA59T human hepatoma cells. Journal of Receptor and Signal Transduction Research 33: 89–95.

    Article  PubMed  CAS  Google Scholar 

  36. Banks, P.A., S. Tenner, E.C. Noordhoek, G. Sica, S. Feng, and M. Zinner. 1996. Does pancreatic necrosis predict severity in patients with acute necrotizing pancreatitis? Digestion 5: 218–223.

    Google Scholar 

  37. Bhatia, M., F.L. Wong, Y. Cao, H.Y. Lau, J. Huang, P. Puneet, and L. Chevali. 2005. Pathophysiology of acute pancreatitis. Pancreatology 5: 132–134.

    Article  PubMed  Google Scholar 

  38. Alhan, E., A. Cinel, C. Ercin, S. Türkyılmaz, B.V. Kural, M. Alper, and D. Flinte. 2011. The effects of p53 inhibition using pifithrin-α on acute necrotizing pancreatitis in rats. Turkish Journal of Medical Sciences 41: 673–683.

    CAS  Google Scholar 

  39. Lotze, M.I., H.J. Zeh, A. Rubartelli, L.J. Sparvero, A.A. Amoscato, N.R. Washburn, M.E. Devera, X. Liang, M. Tör, and T. Billiar. 2007. The grateful dead: Damage-associated molecular pattern molecules and reduction/oxidation regulate immunity. Immunological Reviews 220: 60–81.

    Article  PubMed  CAS  Google Scholar 

  40. Sharif, R., R. Dawra, K. Wasiluk, P. Phillips, V. Dudeja, E. Kurt-Jones, R. Finberg, and A. Saluja. 2009. Impact of toll-like receptor 4 on the severity of acute pancreatitis and pancreatitis-associated lung injury in mice. Gut 58: 813–819.

    Article  PubMed  CAS  Google Scholar 

  41. Alhan, E., C. Türkyılmaz, C. Ercin, B.V. Kural, and D. Flinte. 2012. Does nuclear factor-Kappa B in peripheralmononuclear cells have a prognostic role during acute necrotizing pancreatitis in rats? European Surgical Research 48: 34–39.

    Article  PubMed  CAS  Google Scholar 

  42. Zhang, X., D. Wu, and X. Jiang. 2009. ICAM-1 and acute pancreatitis complicated by acute lung injury. Journal of the Pancreas 10: 8–14.

    PubMed  Google Scholar 

  43. Weidenhach, H., M.M. Lerch, T.M. Gress, D. Pfaff, S. Turi, and G. Adler. 1995. Vasoactive mediators and the progression from edematous to necrotizing experimental acute pancreatitis. Gut 37: 434–440.

    Article  Google Scholar 

  44. Murakami, H., A. Nakao, W. Kishimoto, M. Nakano, and H. Takagel. 1995. Detection of O2 generation and neutrophil accumulation in rat lungs after acute necrotizing pancreatitis. Surgery 118: 547–554.

    Article  PubMed  CAS  Google Scholar 

  45. Ivey, C.L., A.L. Stephenson, and A.M. Townsley. 1998. Involvement of cytochrome P-450 enzyme activity in the control of microvascular permeability in canine lung. American Journal of Physiology. Lung Cellular and Molecular Physiology 275: 756–776.

    Google Scholar 

  46. Thapa, D., J.S. Lee, M.A. Park, M.Y. Cho, Y.J. Park, H.G. Choi, T.C. Jeong, and J.A. Kim. 2009. Inhibitory effects of clotrimazole on TNF-alpha-induced adhesion molecule expression and angiogenesis. Archives of Pharmacal Research 32: 593–603.

    Article  PubMed  CAS  Google Scholar 

  47. Borgström, A., S. Appelros, C.A. Müller, W. Uhl, and M.W. Büchler. 2002. Role of activation peptides from pancreatic proenzymes in the diagnosis and prognosis of acute pancreatitis. Surgery 131: 125–128.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Etem Alhan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cekic, A.B., Alhan, E., Usta, A. et al. Effects of Clotrimazol on the Acute Necrotizing Pancreatitis in Rats. Inflammation 36, 1576–1583 (2013). https://doi.org/10.1007/s10753-013-9702-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-013-9702-3

KEY WORDS

Navigation