Effects of nafamostat mesilate on the prevention of cerulein-induced acute pancreatitis.
OBJECTIVE
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.
Lee
Jun Kyu
JK
Department of Internal Medicine, Dongguk University International Hospital, Dongguk University College of Medicine, Goyang, Korea.
Ryu
Ji Kon
JK
Park
Joo Kyoung
JK
Lee
Sang Hyub
SH
Yoon
Won Jae
WJ
Kim
Yong-Tae
YT
Jung
Hyun Chae
HC
Yoon
Yong Bum
YB
D000681:Amylases / Q000097:blood; D000818:Animals; D001550:Benzamidines; D002108:Ceruletide / Q000633:toxicity; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D008049:Lipase / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009195:Peroxidase / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D001550:Benzamidines; D006146:Guanidines; D015850:Interleukin-6; D011480:Protease Inhibitors; D002108:Ceruletide; D009195:Peroxidase; D048051:p38 Mitogen-Activated Protein Kinases; D008049:Lipase; D000681:Amylases; C032855:nafamostat