A potent angiogenic factor, vascular endothelial growth factor, improves the survival of the on-going acute hepatic failure in rats

Abstract

Although it has been shown that a simultaneous administration of the vascular endothelial growth factor (VEGF); a potent angiogenic factor, could improve the overall survival of chemically induced acute hepatic failure (AHF) in rats, it has not been elucidated yet whether this salvage effect can be observed in the on-going AHF or not. For future clinical application, we examined the effect of VEGF on the on-going AHF. A combination of d-galactosamine (Gal-N) and lipopolysaccharide (LPS) was administered to induce AHF in rats. The survival rate and several indices were compared with or without VEGF treatment at 12 and 24h after the intoxication. Even after the establishment of severe liver injury, the overall survival and the serum ALT elevation were significantly improved by treatment with VEGF. The proliferation of the hepatocytes and sinusoidal endothelial cells (SEC) was also stimulated by VEGF. Furthermore, VEGF prevented the destruction of the architecture of the hepatic sinusoids. Since VEGF significantly improved the survival of the on-going AHF, the exogenous VEGF administration may represent a feasible new therapeutic strategy for AHF in the future.