title: Thalidomide in rat liver cirrhosis: blockade of tumor necrosis factor-alpha via inhibition of degradation of an inhibitor of nuclear factor-kappaB.
abstract: OBJECTIVE
  Thalidomide inhibited tumor necrosis factor-alpha (TNF-alpha) effectively in many trials. The aim of this study was to investigate the effect of thalidomide on the expression of nuclear factor-kappaB (NF-kappaB), inhibitor of NF-kappaB (IkappaB) and TNF-alpha 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-kappaBp65, alpha-smooth muscle actin (alpha-SMA) protein and TNF-alpha mRNA were studied in the liver, IkappaBalpha and TNF-alpha protein in the cytoplasm and NF-kappaBp65 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-alpha mRNA and protein, NF-kappaBp65 and alpha-SMA were significantly decreased and IkappaBalpha protein was also elevated (p < 0.01).
  
  
  CONCLUSIONS
  Thalidomide downregulates NF-kappaB-induced TNF-alpha and activates hepatic stellate cells (HSC) via inhibition of IkappaB degradation to prevent liver cirrhosis.
authors.affiliation: Department of Gastroenterology, Renmin Hospital, Wuhan University, Wuhan, China.
authors.forename: Shelley Chireyath
authors.initials: SC
authors.lastname: Paul
authors.forename: Peng
authors.initials: P
authors.lastname: Lv
authors.forename: Yan-Jv
authors.initials: YJ
authors.lastname: Xiao
authors.forename: Ping
authors.initials: P
authors.lastname: An
authors.forename: Shi-Quan
authors.initials: SQ
authors.lastname: Liu
authors.forename: He-Sheng
authors.initials: HS
authors.lastname: Luo
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects; D006909:Hydroxyproline / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013792:Thalidomide / Q000494:pharmacology* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000199:Actins; D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D002251:Carbon Tetrachloride; D006909:Hydroxyproline; D020672:I-kappa B Proteins; D007166:Immunosuppressive Agents; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B; D012333:RNA, Messenger; D013792:Thalidomide; D014409:Tumor Necrosis Factor-alpha; C000606206:Nfkbia protein, rat; C498862:Acta2 protein, rat