Effects of nafamostat mesilate on the prevention of cerulein-induced acute pancreatitis.

Abstract

OBJECTIVES:

Protease inhibitors showed protective effects on animal models of acute pancreatitis when administered before induction of pancreatitis, and results when administered after induction are uncertain. We assessed the effects of nafamostat mesilate in a mouse model of cerulein-induced pancreatitis comparing results of before and after induction.

METHODS:

Cerulein was injected to mice intraperitoneally to induce pancreatitis, and they received intravenous nafamostat mesilate before and after induction. Serum concentrations of amylase and lipase, histological changes, and tissue expression of myeloperoxidase were measured. In addition, tissue activation of p38 mitogen-activated protein kinase (MAPK) and interleukin-6 was evaluated.

RESULTS:

Development of pancreatitis was prevented by pretreatment with nafamostat mesilate. However, such effect was not shown when given after induction, although it partially suppressed myeloperoxidase expression and infiltration of inflammatory cells. Tissue expression of phospho-p38 MAPK was prominent in mice with pancreatitis and suppressed by pretreatment with nafamostat mesilate. Interleukin-6 expression was not influenced by either cerulein or nafamostat mesilate.

CONCLUSIONS:

The development of pancreatitis was prevented by treating mice with nafamostat mesilate before induction, however, this finding was not observed if administered after injection of cerulein. Pretreatment with nafamostat mesilate suppressed activation of p38 MAPK.

• Authors: Jun Kyu Lee, Ji Kon Ryu, Joo Kyoung Park, Sang Hyub Lee, Won Jae Yoon, Yong-Tae Kim, Hyun Chae Jung, Yong Bum Yoon
• Journal: Pancreas (Pancreas) Vol. 36 Issue 3 Pg. 255-60 (Apr 2008) ISSN: 1536-4828 [Electronic] United States
• PMID: 18362838 (Publication Type: Journal Article)

Chemical References

• Benzamidines
• Guanidines
• Interleukin-6
• Protease Inhibitors
• Ceruletide
• Peroxidase
• p38 Mitogen-Activated Protein Kinases
• Lipase
• Amylases
• nafamostat

Topics

• Amylases (blood)
• Animals
• Benzamidines
• Ceruletide (toxicity)
• Female
• Guanidines (pharmacology)
• Interleukin-6 (metabolism)
• Lipase (blood)
• Mice
• Mice, Inbred BALB C
• Pancreatitis (chemically induced, metabolism, pathology, prevention & control)
• Peroxidase (metabolism)
• Protease Inhibitors (pharmacology)
• p38 Mitogen-Activated Protein Kinases (metabolism)