Abstract
The investigation of the effects of the celecoxib as a cylooxygenase-2 (COX-2) inhibitor on the course of the acute necrotising pancreatitis (ANP) in rats. ANP was induced in 72 rats by standardized intraductal glycodeoxycholic acid infusion and intravenous cerulein infusion. The rats were divided into four groups (six rats in each group): Sham + saline, sham + celecoxib, ANP + saline, ANP + celecoxib. Six hours later after the ANP induction, celecoxib (10 mg/kg) or saline was given i.p. In the 12th hour, routine cardiorespiratuar, renal parameters were monitored to assess the organ function. The serum amylase, alanine amino transferase (ALT), interleukin 6 (IL-6), lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid, the serum concentration of the urea, the tissue activity of myeloperoxidase (MPO) and malondialdehyde (MDA) in pancreas and lungs were measured. The pancreas histology was examined. In the second part of the study, 48 rats were studied in four groups similar to the first part. Survival of all the rats after the induction of ANP was observed for 24 h. The induction of the pancreatitis increased the mortality from 0/12, in the sham groups to 4/12 (30%) in the acute pancreatitis with saline group, 5/12 (42%) in the acute pancreatitis with celecoxib group respectively, heart rate, the serum activities of amylase, ALT, the tissue activities of MPO, MDA in the pancreas and lung, and LDH in BAL fluid, the serum concentration of the urea and IL-6, the degree of the pancreatic damage and decreased the blood pressure, the urine production, pO2 and the serum concentration of calcium. The use of celecoxib did not alter these changes except the serum IL-6 concentration, urine production and MPO, MDA activities in the tissue of the lungs and pancreas. Serum urea concentration and pancreatic damage in ANP + celecoxib group were insignificantly lesser than ANP + saline group. Whereas treatment with celecoxib improves lung and renal functions, the degree of pancreatic damage partially and the serum IL-6 level completely, it does not improve the cardiovascular and liver functions, the mortality rate and the calcium level. Celecoxib may be useful for the support of some organ functions during ANP in rats.
Similar content being viewed by others
References
Alhan, E., R. Cicek, C. Erçin, A. örem, and B. Vanizor. 2002. Effects of the tyrosine kinase inhibitor tyrphostin AG 556 0n acute pancreatitis in rats. Eur. J. Surg. 168: 557–562.
Steer, M. L. 1993. Etiology and pathophysilogy of acute pancreatitis. In: The Pancreas: Biology, Pathophysilogy, and Disease, V. L. V. Go, E. P. Diamagno, J. D. Gardner, E. Lebenthal, A. Reber, and G. A. Scheele, eds. Raven Press, New York, pp. 581–592.
Alhan, E., U. Kücüktülü, C. Ercin, and O. Deger. 2001. The effects of dopexamine on acute necrotizing pancreatitis in rats. Eur. J. Surg. 167(10):761–766.
Norman, J. 1998. The role of cytokines in the pathogenesis of acute pancreatitis. Am. J. Surg. 1175: 76–83.
Lankisch, P. G., H. Koop, H. Winckler, and W. Vogt. 1978. Indometacin treatment of acute experimental pancreatitis in the rat. Scand. J. Gastroenterol. 13: 629–633.
Closa, D., J. Roello-Catafau, G. Hotter, O. Bulbena, L. Fernandez-Cruz, and E. Gelpi. 1993. Cyclooxygenase and lipooxygenase metabolism in sodium taurocholat induced acute hemorrhagic pancreatitis in rats. Prostaglandin 45: 315–22.
Stanfield, N. J., and V. V. Kakkar. 1983. Prostoglandins and acute pancreatitis—Experimental and clinical studies. Br. J. Surg. 70: 573–576.
Yücel, K., E. Alhan, U. Küçüktülü, M. Piri, E. Ercin, and O. Deger. 2002. The effects of prostaglandin E1 on the microperfusion of the pancreas during acute necrotizing pancreatitis in rats. Hepato-Gastroenterology 49: 544–548.
Lefkowith, J. B. 1999. Cylooxygenase-2 specifity and its clinical implications. Excerpt. Med. 106: 43S–53S.
Zabel-langhennig, A., B. Holler, K. Engeland, and J. Mossner. 1999. Cylooxygenase-2 transcription is stimulated and amylase secretion is inhibited in pancreatic acinar cells after induction of acute pancreatitis. Biochem. Biophys. Res. Commun. 265: 545–549.
Ethridge, R. T., D. H. Chung, M. Slogoff, R. A. Ehlers, M. R. Hellmich, S. Rajaraman, H. Saito, T. Uchida, and B. M. Evers. 2002. Cylooxygenase-2 gene disruption attenuates the severity of pancreatitis and pancreatitis—Associated lung injury. Gastroenterology 123: 1311–1322.
Foitzik, T., H. G. Hotz, B. Hotz, F. Wittig, and H. J. Buhr. 2003. Selective inhibition of cylooygenase-2 (COX-2) reduces prostaglandin E2 production and attenuates systemic disease squeal in experimental pancreatitis. Hepato-Gastroenterology 50: 1159–1162.
Song, A. M., L. Bhagat, V. P. Singh, G. G. Van Acker, M. L. Ster, and A. K. Saluja. 2002. Inhibition of cylooxygenase-2 ameliorates the severity of pancreatitis and associated lung injury. Am. J. Physiol. Gastrointest. Liver Physiol. 28: G1166–-G1174.
Carrillo-Jimenez, R., and M. Nurberger. 2000. Celecoxib-induced acute pancreatitis and hepatitis. Arch. Int. Med. 160: 553–554.
Schmidt, J., M. D. Rattner, and K. Lewandrowski. 1992. A better model of acute pancreatitis for evaluating therapy. Ann. Surg. 215: 44–56.
Sookhal, S., J. J. Wang, and M. McCourt. 2002. A novel therapeutic strategy for attenuating neutrophil-mediated lung injury in vivo. Ann. Surg. 235: 283–291.
Lankisch, P. G., U. Pohl, and J. Otto. 1988. When should treatment of acute experimental pancreatitis be started? The early phase of bile-induced acute pancreatitis. Res. Exp. Med. 188: 123–129.
Rau, B., B. Poch, and F. Gansauge. 2000. Pathophysiologic role of oxygen free radicals in acute pancreatitis. Ann. Surg. 31: 352–360.
Banks, P. A., S. Tenner, and E. C. Noordhoek. 1996. Does pancreatic necrosis predict severity in-patients with acute necrotizing pancreatitis? Digestion 57: 218.
Murakami, H., A. Nakao, and W. Kishimoto. 1995. Detection of O2− generation and neutrophil accumulation in rat lungs after acute necrotizing pancreatitis. Surgery 118: 547–554.
Malik, A. B., M. B. Periman, J. A. Cooper, T. Neonan, and R. Bizios. 1985. Pulmonar microvascular effects of arachiodonic acid metabolites and their role in lung injury. Fed. Proc. 44: 36–41.
Weidenhach, H., M. M. Lerch, and T. M. Gress. 1995. Vasoactive mediators and the progression from edematous to necrotizing experimental acute pancreatitis. Gut 37: 434–440.
Osvaldt, A. B., P. Viero, M. S. Borges da Costa, L. R. Wendt, V. P. Bersch, and L. Rohde. 2001. Evaluation of Ranson, Glasgow, APACHE-II, and APACHE-O criteria to predict severity in pancreatitis. Int. Surg. 86(3):158–161.
Blume, C., G. Heise, A. Muhlfeld, D. Bach, K. Schror, C. D.Gerhardz, B. Grabensee, and P. Hearing. 1999. Effect of flosulide, a selective cyclooxygenase 2 inhibitor, an passive Heymann nephritis in the rat. Kidney Int. 56: 1770–1778.
Borgström, A., S. Appelros, and C. A. Müller. 2002. Role of activation peptides from pancreatic proenzymes in the diagnosis and prognosis of acute pancreatitis. Surgery 131: 125–128.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Alhan, E., Kalyoncu, N.I., Ercin, C. et al. Effects of the Celecoxib on the Acute Necrotizing Pancreatitis in Rats. Inflammation 28, 303–309 (2004). https://doi.org/10.1007/s10753-004-6055-x
Issue Date:
DOI: https://doi.org/10.1007/s10753-004-6055-x