Salvage effect of the vascular endothelial growth factor on chemically induced acute severe liver injury in rats

Background/Aims: 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. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.