Suramin prevents fulminant hepatic failure resulting in reduction of lethality through the suppression of NF-kappaB activity.
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.
Goto
Takashi
T
Department of Gastroenterology, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan. takashi@doc.med.akita-u.ac.jp
Takeuchi
Satoko
S
Miura
Kouichi
K
Ohshima
Shigetoshi
S
Mikami
Ken-ichiro
K
Yoneyama
Kazuo
K
Sato
Michiko
M
Shibuya
Tomomi
T
Watanabe
Daisuke
D
Kataoka
Ei
E
Segawa
Daisuke
D
Endo
Ayako
A
Sato
Wataru
W
Yoshino
Ryutaro
R
Watanabe
Sumio
S
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
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