Reversal Effect of Thalidomide on Established Hepatic Cirrhosis in Rats via Inhibition of Nuclear Factor-κB/Inhibitor of Nuclear Factor-κB Pathway

Background ssion of nuclear factor-κB (NF-κB)/inhibitor of nuclear factor-κB (IκB) signaling pathway is a potential property of thalidomide. This study was designed to investigate the effects of thalidomide on expressions of NF-κB, IκB and intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule (VCAM-1) in established rat liver cirrhosis. s ver cirrhosis was achieved by IP injection of carbon tetrachloride (CCl4) three times weekly for 8 weeks. CCl4 was then discontinued and thalidomide (100 mg/kg) or its vehicle was administered daily by gavage for 6 weeks. Hydroxyproline (HYP) content in liver was detected by biochemical assay. NF-κBp65, ICAM-1, VCAM-1 and α-smooth muscle actin (α-SMA) protein in the liver, IκBα protein in cytoplasm and NF-κBp65 protein in nucleus and ICAM-1, VCAM-1 mRNA levels in the liver were studied using immunohistochemistry, Western blot, and reverse transcriptase polymerase chain reaction, respectively. s ed with the spontaneous recovery of cirrhosis, the histopathology of liver of rats given thalidomide was significantly improved. HYP content in liver, the expressions of ICAM-1, VCAM-1 mRNA and protein, NF-κBp65 and α-SMA protein were decreased significantly and IκBα protein in liver was elevated significantly in this group. sions omide may exert its effect on downregulation of NF-κB-induced adhesion molecules and activation of hepatic stellate cell via inhibition of degradation of IκB to reverse established rat hepatic cirrhosis.