title: Salvage effect of the vascular endothelial growth factor on chemically induced acute severe liver injury in rats.
abstract: OBJECTIVE
  The role of the vascular endothelial growth factor (VEGF), a potent angiogenic factor, in liver regeneration following acute severe liver injury (ALI) has not been elucidated. The aims of the current study were to investigate the role of VEGF, and to find out whether VEGF can improve the outcome of ALI in rats.
  
  
  METHODS
  ALI was induced in male rats by combination of D-galactosamine (Gal-N) and lipopolysaccharide (LPS). The survival rate and several indices were chronologically compared with or without VEGF treatment.
  
  
  RESULTS
  The overall survival rate of the VEGF-treated group significantly improved as compared with the untreated group (100 vs. 27%, respectively). The serum ALT elevation, with a peak at 24 h after Gal-N+LPS intoxication, was markedly attenuated with VEGF treatment. The proliferation of hepatocytes and sinusoidal endothelial cells (SEC) was stimulated by VEGF with a peak at 36 and 96 h, respectively. The immunohistochemical analysis revealed that VEGF drastically prevented destruction of the SEC architecture in ALI. Our in vitro study showed that VEGF significantly prevented the Gal-N+LPS-induced cytotoxicity and apoptosis of SEC.
  
  
  CONCLUSIONS
  VEGF treatment significantly reduced the mortality rate of ALI in the rat, and it may provide a new therapeutic strategy for ALI.
authors.affiliation: Third Department of Internal Medicine, Nara Medical University, School of Medicine, Shijo-cho 840, Kashihara, Nara 634-8522, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Namisaki
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yoshiji
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Kojima
authors.forename: Junichi
authors.initials: J
authors.lastname: Yoshii
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Ikenaka
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Noguchi
authors.forename: Shinya
authors.initials: S
authors.lastname: Sakurai
authors.forename: Koji
authors.initials: K
authors.lastname: Yanase
authors.forename: Mitsuteru
authors.initials: M
authors.lastname: Kitade
authors.forename: Masaharu
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Asada
authors.forename: Masahito
authors.initials: M
authors.lastname: Uemura
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Nakamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukui
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D005688:Galactosamine / Q000633:toxicity; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000633:toxicity; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D051381:Rats; D016879:Salvage Therapy / Q000379:methods*; D015996:Survival Rate; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D008070:Lipopolysaccharides; D042461:Vascular Endothelial Growth Factor A; D005688:Galactosamine