BACKGROUND: Suppression of nuclear factor-kappaB (NF-kappaB)/inhibitor of nuclear factor-kappaB (IkappaB) signaling pathway is a potential property of thalidomide. This study was designed to investigate the effects of thalidomide on expressions of NF-kappaB, IkappaB and intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule (VCAM-1) in established rat liver cirrhosis. METHODS: Rat 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-kappaBp65, ICAM-1, VCAM-1 and alpha-smooth muscle actin (alpha-SMA) protein in the liver, IkappaBalpha protein in cytoplasm and NF-kappaBp65 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. RESULTS: Compared 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-kappaBp65 and alpha-SMA protein were decreased significantly and IkappaBalpha protein in liver was elevated significantly in this group. CONCLUSIONS: Thalidomide may exert its effect on downregulation of NF-kappaB-induced adhesion molecules and activation of hepatic stellate cell via inhibition of degradation of IkappaB to reverse established rat hepatic cirrhosis.
BACKGROUND: Suppression of nuclear factor-kappaB (NF-kappaB)/inhibitor of nuclear factor-kappaB (IkappaB) signaling pathway is a potential property of thalidomide. This study was designed to investigate the effects of thalidomide on expressions of NF-kappaB, IkappaB and intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule (VCAM-1) in established ratliver cirrhosis. METHODS:Ratliver 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-kappaBp65, ICAM-1, VCAM-1 and alpha-smooth muscle actin (alpha-SMA) protein in the liver, IkappaBalpha protein in cytoplasm and NF-kappaBp65 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. RESULTS: Compared 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-kappaBp65 and alpha-SMA protein were decreased significantly and IkappaBalpha protein in liver was elevated significantly in this group. CONCLUSIONS:Thalidomide may exert its effect on downregulation of NF-kappaB-induced adhesion molecules and activation of hepatic stellate cell via inhibition of degradation of IkappaB to reverse established rathepatic cirrhosis.
Authors: Nicholas G Theodorakis; Yining N Wang; Vyacheslav A Korshunov; Mary A Maluccio; Nicholas J Skill Journal: World J Gastroenterol Date: 2015-04-14 Impact factor: 5.742
Authors: Len Verbeke; Inge Mannaerts; Robert Schierwagen; Olivier Govaere; Sabine Klein; Ingrid Vander Elst; Petra Windmolders; Ricard Farre; Mathias Wenes; Massimiliano Mazzone; Frederik Nevens; Leo A van Grunsven; Jonel Trebicka; Wim Laleman Journal: Sci Rep Date: 2016-09-16 Impact factor: 4.379