Effects of thalidomide on the expression of NF-κB and TNF-α in experimental hepatic fibrotic rats

AIM: To study the effects of thalidomide on the expressions of nuclear factor κB (NF-κB) and tumor necrosis factor-α (TNF-α) in rat liver fibrosis.METHODS: The fibrosis of rat liver was induced by intraperitoneal injection of carbon tetrachloride thrice weekly.Meanwhile thalidomide (10 mg·kg^-1·d^-1 or 100 mg·kg^-1·d^-1) was given daily by the intragastric route for 8 weeks.Serum alanine aminotransferase (ALT),aspartate aminotransferase (AST),prealbumin (PA),hyaluronic acid (HA) and laminin (LN),and hydroxyproline (HYP) contents in the liver,NF-κB p65 and α-smooth muscle actin (α-SMA) protein in the liver,IκBα and TNF-α protein in cytoplasm and NF-κB p65 protein in nucleus and TNF-α mRNA levels in the liver were studied.RESULTS: Compared with the model group,the Knodell score,serum ALT,AST,HA,LN levels and HYP contents in liver,NF-κB p65 protein in nucleus and α-SMA protein in the liver,and TNF-α mRNA and protein in the liver of rats given high dose of thalidomide were decreased significantly (P<0.01).Meanwhile PA level and IκBα protein in cytoplasm were elevated significantly (P<0.01).CONCLUSION: Thalidomide exerts its effect on the down-regulation of NF-κB-induced TNF-α via inhibiting dissociation and degradation of IκB and prevents liver fibrosis in rats.