title: Antithrombin III injection via the portal vein suppresses liver damage.
abstract: OBJECTIVE
  To investigate the effects of antithrombin III (AT III) injection via the portal vein in acute liver failure.
  
  
  METHODS
  Thirty rats were intraperitoneally challenged with lipopolysaccharide (LPS) and D-galactosamine (GalN) and divided into three groups: a control group; a group injected with AT III via the tail vein; and a group injected with AT III via the portal vein. AT III (50 U/kg body weight) was administrated 1 h after challenge with LPS and GalN. Serum levels of inflammatory cytokines and fibrin degradation products, hepatic fibrin deposition, and hepatic mRNA expression of hypoxia-related genes were analyzed.
  
  
  RESULTS
  Serum levels of alanine aminotransferase, tumor necrosis factor-α and interleukin-6 decreased significantly following portal vein AT III injection compared with tail vein injection, and control rats. Portal vein AT III injection reduced liver cell destruction and decreased hepatic fibrin deposition. This treatment also significantly reduced hepatic mRNA expression of lactate dehydrogenase and heme oxygenase-1.
  
  
  CONCLUSIONS
  A clinically acceptable dose of AT III injection into the portal vein suppressed liver damage, probably through its enhanced anticoagulant and anti-inflammatory activities.
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. mmasayuk@intmed3.med.kyushu-u.ac.jp
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Masaki
authors.initials: M
authors.lastname: Kato
authors.forename: Masatake
authors.initials: M
authors.lastname: Tanaka
authors.forename: Kosuke
authors.initials: K
authors.lastname: Tanaka
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Takao
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Kohjima
authors.forename: Tetsuhide
authors.initials: T
authors.lastname: Ito
authors.forename: Munechika
authors.initials: M
authors.lastname: Enjoji
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamuta
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kotoh
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Takayanagi
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage*; D000990:Antithrombin III / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005337:Fibrin / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics; D007267:Injections; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017114:Liver Failure, Acute / Q000517:prevention & control*; D008297:Male; D011169:Portal Vein / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000925:Anticoagulants; D012333:RNA, Messenger; D000990:Antithrombin III; D005337:Fibrin; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat