Suramin prevents fulminant hepatic failure resulting in reduction of lethality through the suppression of NF-κB activity

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)-α, and interleukin (IL)-6 levels were measured. We compared with survival rate, histological found and NF-κB activity between with and without treatment of suramin. In macrophage like cell line, TNF-α and IL-6 production, TNF-α and IL-6 mRNA expression, and NF-κB 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-α, IL-6 levels and NF-κB activity in the liver were significantly lower in mice administered suramin. In an in vitro model, suramin preincubation inhibited TNF-α and IL-6 production, TNF-α and IL-6 mRNA expression, and NF-κB activity. Conclusions Suramin inhibits TNF-α and IL-6 production through the suppression of NF-κB activity from macrophages and shows therapeutic effects on acute liver damage.