title: Suramin prevents fulminant hepatic failure resulting in reduction of lethality through the suppression of NF-kappaB activity.
abstract: OBJECTIVE
  Suramin is a symmetrical polysulfonated naphthylamine derivative of urea. There have been few studies on the effect of suramin on cytokines. We examined the effects of suramin on production of inflammatory cytokines.
  
  
  METHODS
  We made an acute liver injury model treated with d-galactosamine (GalN) and lipopolysaccharide (LPS). Plasma AST, ALT, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 levels were measured. We compared with survival rate, histological found and NF-kappaB activity between with and without treatment of suramin. In macrophage like cell line, TNF-alpha and IL-6 production, TNF-alpha and IL-6 mRNA expression, and NF-kappaB activity was measured.
  
  
  RESULTS
  The lethality of mice administered suramin with GalN/LPS was significantly decreased compared with that in mice without suramin. Changes of hepatic necrosis and apoptosis were slight in suramin-treated mice. Serum AST, ALT, TNF-alpha, IL-6 levels and NF-kappaB activity in the liver were significantly lower in mice administered suramin. In an in vitro model, suramin preincubation inhibited TNF-alpha and IL-6 production, TNF-alpha and IL-6 mRNA expression, and NF-kappaB activity.
  
  
  CONCLUSIONS
  Suramin inhibits TNF-alpha and IL-6 production through the suppression of NF-kappaB activity from macrophages and shows therapeutic effects on acute liver damage.
authors.affiliation: Department of Gastroenterology, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan. takashi@doc.med.akita-u.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Goto
authors.forename: Satoko
authors.initials: S
authors.lastname: Takeuchi
authors.forename: Kouichi
authors.initials: K
authors.lastname: Miura
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Ohshima
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Mikami
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yoneyama
authors.forename: Michiko
authors.initials: M
authors.lastname: Sato
authors.forename: Tomomi
authors.initials: T
authors.lastname: Shibuya
authors.forename: Daisuke
authors.initials: D
authors.lastname: Watanabe
authors.forename: Ei
authors.initials: E
authors.lastname: Kataoka
authors.forename: Daisuke
authors.initials: D
authors.lastname: Segawa
authors.forename: Ayako
authors.initials: A
authors.lastname: Endo
authors.forename: Wataru
authors.initials: W
authors.lastname: Sato
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Yoshino
authors.forename: Sumio
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D005688:Galactosamine; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides; D008099:Liver / Q000473:pathology; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000401:mortality / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D013498:Suramin / Q000494:pharmacology*; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D013498:Suramin; D005688:Galactosamine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase