title: Sivelestat sodium hydrate inhibits neutrophil migration to the vessel wall and suppresses hepatic ischemia-reperfusion injury.
abstract: BACKGROUND
  Sivelestat sodium hydrate (sivelestat) is a specific neutrophil elastase inhibitor that is effective in treating acute lung injury associated with systemic inflammatory response syndrome. As such, it may be useful in treating hepatic ischemia-reperfusion injury (IRI), a condition in which neutrophils transmigrate into the interstitium, leading to release of neutrophil elastase from neutrophils and consequent damage to the affected tissue, particularly in cases of hepatic failure after liver transplantation or massive liver resection.
  
  
  OBJECTIVE
  The purpose of this study was to examine whether treatment with sivelestat inhibits neutrophil adhesion and migration to the vessel wall and suppresses hepatic IRI.
  
  
  METHODS
  Whether and, if so, the extent to which sivelestat suppresses the adhesion and migration of neutrophils and reduces liver damage in hepatic IRI was examined in a human umbilical vein endothelial cell (HUVEC) model and a rat hepatic IRI model.
  
  
  RESULTS
  In the HUVEC model, the extent of the adhesion and migration of neutrophils stimulated by platelet-activating factor were found to be dose-dependently inhibited by sivelestat treatment (p < 0.05). In the rat model, serum liver enzyme levels were significantly lower at 12 h after reperfusion, and the number of neutrophils that had migrated to extravascular sites was significantly less in the treatment group compared to the control group (p < 0.05).
  
  
  CONCLUSIONS
  Sivelestat inhibits the adhesion and migration of neutrophils to vascular endothelium in hepatic IRI, thereby suppressing liver injury.
authors: Division of Cancer Medicine, Department of Gastroenterological Surgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan, s-sakai@staff.kanazawa-u.ac.jp.
authors: Seisho
authors: S
authors: Sakai
authors: Hidehiro
authors: H
authors: Tajima
authors: Tomoharu
authors: T
authors: Miyashita
authors: Shin-Ichi
authors: S
authors: Nakanuma
authors: Isamu
authors: I
authors: Makino
authors: Hironori
authors: H
authors: Hayashi
authors: Hisatoshi
authors: H
authors: Nakagawara
authors: Hirohisa
authors: H
authors: Kitagawa
authors: Sachio
authors: S
authors: Fushida
authors: Takashi
authors: T
authors: Fujimura
authors: Hidehito
authors: H
authors: Saito
authors: Seiichi
authors: S
authors: Munesue
authors: Yasuhiko
authors: Y
authors: Yamamoto
authors: Tetsuo
authors: T
authors: Ohta
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007154:Immune System Diseases; D007960:Leukocyte Disorders; D008107:Liver Diseases / Q000517:prevention & control*; D008297:Male; D009504:Neutrophils / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D018746:Systemic Inflammatory Response Syndrome / Q000517:prevention & control
chemical_list: D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; C069195:sivelestat; D005998:Glycine