title: Antithrombin prevents apoptosis by regulating inflammation in the liver in a model of cold ischemia/warm reperfusion injury.
abstract: OBJECTIVE
  Hepatic ischemia-reperfusion injury is a major problem in liver surgery. To modulate the complex process of inflammation, additional drugs to add to well-defined organ preserving solutions have been sought. The aim of the current study was to investigate the additive potential of antithrombin (AT) in liver preservation.
  
  
  METHODS
  Female Wistar rats were randomized into four groups: sham (Group I), experiment model (Group II), and treatment groups with AT (250U/kg) administration systematically (Group III) or locally (Group IV) before hepatectomy. UW solution was used for liver preservation for 24h at 4°C. The livers in group II, III and IV were reperfused 1h and histopathological parameters were evaluated microscopically. Apoptosis was assessed with TUNEL test.
  
  
  RESULTS
  Karyorrhexis was lower in the local treatment with AT group. Sinusoidal desquamation and mononuclear cell infiltration was higher in the experimental model group. Sinusoidal enlargement was higher in the systemic AT treatment group and neutrophil infiltration to sinusoids was lowest in the local treatment group. Apoptosis of hepatocytes and sinusoidal cells were significantly suppressed in rats that were treated with AT via portal vein infusion.
  
  
  CONCLUSIONS
  AT treatment obviously contributed to liver preservation in our model; the effects on apoptosis and inflammation were prominent. Therefore, AT should be considered as a potent agent although its clinical role has yet to be defined in ex-vivo hepatic preservation.
authors.affiliation: Department of General Surgery, Ordu University, Ordu, Turkey. isiksevil@hotmail.com
authors.forename: Sevil
authors.initials: S
authors.lastname: Isik
authors.forename: Pars
authors.initials: P
authors.lastname: Tuncyurek
authors.forename: Neslihan Inci
authors.initials: NI
authors.lastname: Zengin
authors.forename: Ali Eba
authors.initials: AE
authors.lastname: Demirbag
authors.forename: Fuat
authors.initials: F
authors.lastname: Atalay
authors.forename: Sezai
authors.initials: S
authors.lastname: Yilmaz
authors.forename: Taner
authors.initials: T
authors.lastname: Orug
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000991:Antithrombins / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D050377:Cold Ischemia; D019610:Cytoprotection; D004195:Disease Models, Animal; D005260:Female; D006498:Hepatectomy; D006505:Hepatitis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D020287:In Situ Nick-End Labeling; D007262:Infusions, Intravenous; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000276:immunology / Q000473:pathology / Q000601:surgery; D020556:Neutrophil Infiltration / Q000187:drug effects; D011169:Portal Vein; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D013623:Tail / Q000098:blood supply; D052096:Warm Ischemia
chemical_list: D000893:Anti-Inflammatory Agents; D000991:Antithrombins