Background/Aims: Thalidomide inhibited tumor necrosis factor-α (TNF-α) effectively in many trials. The aim of this study was to investigate the effect of thalidomide on the expression of nuclear factor-ĸB (NF-ĸB), inhibitor of NF-ĸB (IĸB) and TNF-α in a rat model of liver cirrhosis. Methods: Liver cirrhosis was achieved by intraperitoneal injection of carbon tetrachloride thrice weekly, and thalidomide (10 or 100 mg/kg/day) was given daily by intragastric route for 8 weeks. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), prealbumin (PA), hyaluronic acid (HA) and laminin (LN), and hydroxyproline (HYP), NF-ĸBp65, α-smooth muscle actin (α-SMA) protein and TNF-α mRNA were studied in the liver, IĸBα and TNF-α protein in the cytoplasm and NF-ĸBp65 protein in the nucleus. Results: Compared with nontreated cirrhotic rats, the histopathology of rats given thalidomide (100 mg/kg) was significantly better. Serum ALT, AST, HA and LN and HYP content in the liver were significantly decreased and PA was elevated (p < 0.01) in this group; the expression of TNF-α mRNA and protein, NF-ĸBp65 and α-SMA were significantly decreased and IĸBα protein was also elevated (p < 0.01). Conclusion: Thalidomide downregulates NF-ĸB-induced TNF-α and activates hepatic stellate cells (HSC) via inhibition of IĸB degradation to prevent liver cirrhosis.
This study was to evaluate the effects of thalidomide on expression of adhesion molecules in liver cirrhosis. The cirrhosis was induced in Wistar rats by intraperitoneal injection of CCl 4 , and thalidomide (10 mg/kg/day or 100 mg/kg/day) was given by intragastric administration for 8 weeks. Liver histopathology and immunohistochemistry were significantly improved and the expressions of ICAM-1, VCAM-1, E-selectin, and TNF-α mRNA and protein were decreased significantly in rats treated with a high dose of thalidomide. Close positive correlation was observed in the expression of the TNF-α mRNA and that of ICAM-1, VCAM-1, and Eselectin mRNA, respectively. These results indicate that thalidomide exerts its effect on the downregulation of adhesion molecules via TNF-α signaling pathway to inhibit liver fibrosis.
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