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