Effect of thalidomide on the expression of vascular endothelial growth factor in a rat model of liver regeneration

Liver regeneration is an angiogenesis-associated phenomenon. The present study investigated the influence of thalidomide, an antiangiogenic agent, on vascular endothelial growth factor (VEGF) expression and liver regeneration after 70% partial hepatectomy (PH) in rats. PH was performed on 50 rats dosed with either thalidomide (100 mg/kg) or a vehicle (controls) by intragastric administration. Serial changes in hepatic microcirculation were evaluated by laser Doppler flowmetry. The VEGF expression in liver tissue was assessed by immunohistochemical study and western blot analysis. Following hepatectomy, the liver regeneration rate increased markedly and reached a peak at 96 h in the two groups. Thalidomide did not affect the overall restoration of liver mass, although a delay in cell proliferation was observed. Prior to PH, the liver microcirculation in rats treated with thalidomide for 2 days was comparatively less than that in their corresponding controls; however, no significant difference between the groups was detected at any time-point following PH. Western blotting showed that the expression of VEGF was upregulated by hepatectomy and the expression levels in the two groups were equal at all studied time-points. The immunohistochemical staining revealed a waved pattern of VEGF expression which advanced from the periportal to pericentral area in both groups, but a slower advancement was detected in thalidomide-treated rats. In conclusion, thalidomide exerted no significant effects on the expression of VEGF and did not impair the overall restoration of liver mass in a rat model of PH-induced liver regeneration, providing supportive evidence for its use as an adjunct treatment modality for liver cancers.