International Journal of Pancreatology

, Volume 29, Issue 3, pp 163–171 | Cite as

Effects of mast-cell stabilization in cerulein-induced acute pancreatitis in rats

  • Nadir Yönetçi
  • Nevin OruçEmail author
  • A. Ömer Özütemiz
  • Handan Ak çelik
  • Gül Yüce


Aim. In this study we aimed to clarify the role of mast cells in the development and progression of inflammation in cerulein-induced acute pancreatitis (AP) in rats. We have also examined the effects of ketotifen; a mast-cell stabilizing agent in the treatment of acute pancreatitis and its relation with nitric oxide (NO) synthesis.

Methods. In the first part of the study we planned to examine the effects mast cell stabilization in acute pancreatitis, while the second part was focused on examining the relation between NO synthesis and the potential effects of ketotifen in AP. Wistar albino rats were randomly divided into 6 groups (n: 10). In the first part of the study, AP was induced by four subcutaneous (sc) injections of 20 µg/kg body weight of cerulein at hourly intervals in Groups A and B while Group C was treated with saline as the control group. Group B was pretreated with ketotifen 1 mg/kg (ip). In the second part, the study design was similar except for the inhibition of nitric oxide synthesis by N-nitro L-arginine methyl ester (L-NAME) 30 mg/kg (ip) in Groups D, E and F. Group D was treated with L-NAME and cerulein and Group E was treated with ketotifen, L-NAME and cerulein. Group F was treated with L-NAME and saline as the control group. Serum amylase activity and pancreatic myeloperoxidase activity (MPO) were measured. Pancreatic histology and mast-cell count in pancreatic tissue were evaluated.

Results. Mast cell count was found to be increased in the pancreatic tissue in cerulein-induced AP. (2.93±0.26 vs 1.98±0.26; p<0.001). Ketotifen treatment significantly reduced cerulein induced edema (1.30±0.21 vs 0.70±0.15; p<0.001), neutrophil infiltration (1.50±0.16 vs 0.60±0.16; p<0.001) and attenuated the increase in amylase (4394.0±149.5 U/L vs 3350.5±216.9 U/L; p<0.05) and MPO activity (1.14±0.13 U/gr tissue vs 0.54±0.08 U/gr tissue; p<0.001). Mast-cell count in pancreatic tissue was also decreased significantly with ketotifen pretreatment (2.93±0.26 vs 1.70±0.21; p<0.05). Inhibition of NO synthesis with L-NAME treatment decreased the beneficial effects of ketotifen.

Conclusion. It seems likely that mast cell activity may play an important role in the initiation and progression of acute pancreatitis. Ketotifen treatment may reduce the severity of AP in rats. The protective action of ketotifen in cerulein-induced acute pancreatitis is most probably owing to mast cell stabilization and stimulation of NO synthesis.

Key Words

Acute pancreatitis ketotifen mast cell Nitric oxide MPO L-NAME 


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Copyright information

© Humana Press Inc. 2002

Authors and Affiliations

  • Nadir Yönetçi
    • 1
  • Nevin Oruç
    • 4
    Email author
  • A. Ömer Özütemiz
    • 4
  • Handan Ak çelik
    • 2
  • Gül Yüce
    • 3
  1. 1.Department of Gastroenterology-DenizliPamukkale UniversityTurkey
  2. 2.Ege University Department of BiochemistryTurkey
  3. 3.Ege University Department of Pathology-IzmirTurkey
  4. 4.Faculty of Medicine, Gastroenterology Department, Izmir-TurkeyEge UniversityBornova-IzmirTurkey

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