title: Effects of nafamostat mesilate on the prevention of cerulein-induced acute pancreatitis.
abstract: 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.
authors: Department of Internal Medicine, Dongguk University International Hospital, Dongguk University College of Medicine, Goyang, Korea.
authors: Jun Kyu
authors: JK
authors: Lee
authors: Ji Kon
authors: JK
authors: Ryu
authors: Joo Kyoung
authors: JK
authors: Park
authors: Sang Hyub
authors: SH
authors: Lee
authors: Won Jae
authors: WJ
authors: Yoon
authors: Yong-Tae
authors: YT
authors: Kim
authors: Hyun Chae
authors: HC
authors: Jung
authors: Yong Bum
authors: YB
authors: Yoon
mesh_terms: 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
chemical_list: 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