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

BackgroundSuppression 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.MethodsRat liver 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.ResultsCompared 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.ConclusionsThalidomide 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.