Salvage effect of the vascular endothelial growth factor on chemically induced acute severe liver injury in rats.
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.
Namisaki
Tadashi
T
Third Department of Internal Medicine, Nara Medical University, School of Medicine, Shijo-cho 840, Kashihara, Nara 634-8522, Japan.
Yoshiji
Hitoshi
H
Kojima
Hideyuki
H
Yoshii
Junichi
J
Ikenaka
Yasuhide
Y
Noguchi
Ryuichi
R
Sakurai
Shinya
S
Yanase
Koji
K
Kitade
Mitsuteru
M
Yamazaki
Masaharu
M
Asada
Kiyoshi
K
Uemura
Masahito
M
Nakamura
Mitsutoshi
M
Fukui
Hiroshi
H
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*
D008070:Lipopolysaccharides; D042461:Vascular Endothelial Growth Factor A; D005688:Galactosamine