Korean J Med.  2007 Apr;72(4):340-351.

The effect of nafamostat mesilate on the prevention of cerulein-induced acute pancreatitis

• Lee JK
• Park JK
• Lee SH
• Yoon WJ
• Ryu JK
• Kim YT
• Jung HC
• Yoon YB

Abstract

BACKGROUND: Many protease inhibitors show a protective effect for acute pancreatitis as seen in animal models. In previous studies, the protease inhibitors were administered before induction of pancreatitis, and there are few published reports examining effects when these agents were administered after induction of pancreatitis. The timing of drug administration may provide an explanation for the ineffectiveness of protease inhibitors for the treatment of patients with acute pancreatitis. Herein, we assessed the protective effect of nafamostat mesilate (NM), a potent protease inhibitor, in a mouse model of cerulean-induced pancreatitis and compared the results of administering the drug before and after the induction of pancreatitis.
METHODS
Cerulein, a cholecystokinin analogue, was injected into mice intraperitoneally to induce pancreatitis. The mice received intravenous NM administration before and after the induction of pancreatitis. The serum concentration of amylase and lipase was measured, histological changes were measured, and the tissue expression of myeloperoxidase was measured to assess the degree of inflammation. Expression of p38 MAPK (mitogen-activated protein kinase), phospho-p38 MAPK, and IL-6 (interleukin-6) in tissue was evaluated.
RESULTS
Acute pancreatitis was induced successfully by intraperitoneal injection of cerulein. Acute pancreatitis could be prevented when NM was administered before the induction of pancreatits. However, the effect was not guaranteed when given after the induction of pancreatitis. For a group of mice with induced pancreatitis, tissue expression of phospho-p38 MAPK was prominent and there was no marked difference in the expression of IL-6 between groups with or without induced pancreatitits.
CONCLUSIONS
Although the efficacy of NM for treatment of acute pancreatitis is doubtful, pretreatment with NM for an expected condition like endoscopic retrograde cholangiopancreatography (ERCP), might be helpful for the prevention of pancreatitis.

Keyword

Acute pancreatitis; Protease inhibitor; Nafamostat; Cerulein; ERCP

MeSH Terms

Amylases
Animals
Ceruletide
Cholangiopancreatography, Endoscopic Retrograde
Cholecystokinin
Humans
Inflammation
Injections, Intraperitoneal
Interleukin-6
Lipase
Mesylates*
Mice
Models, Animal
p38 Mitogen-Activated Protein Kinases
Pancreatitis*
Peroxidase
Protease Inhibitors
Amylases
Ceruletide
Cholecystokinin
Interleukin-6
Lipase
Mesylates
Peroxidase
Protease Inhibitors
p38 Mitogen-Activated Protein Kinases