Effects of mast-cell stabilization in cerulein-induced acute pancreatitis in rats.
OBJECTIVE
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 microg/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.


CONCLUSIONS
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.
Yönetçi
N
N
Pamukkale University, Department of Gastroenterology, Denizli, Turkey.
Oruç
N
N
Ozütemiz
A O
AO
Celik
H A
HA
Yüce
G
G
D000208:Acute Disease; D000818:Animals; D018926:Anti-Allergic Agents / Q000627:therapeutic use; D002108:Ceruletide; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D007665:Ketotifen / Q000627:therapeutic use; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use; D010195:Pancreatitis / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar
D018926:Anti-Allergic Agents; D004791:Enzyme Inhibitors; D002108:Ceruletide; D019331:NG-Nitroarginine Methyl Ester; D007665:Ketotifen