Recombinant human soluble thrombomodulin improved lipopolysaccharide/d-galactosamine-induced acute liver failure in mice

The effect of recombinant human soluble thrombomodulin (tm-α) on acute liver failure (alf) is unclear,and we elucidated the effect of tm-α in lipopolysaccharide (lps)/d-galactosamine (galn)-induced alf in mice. placebo (saline) or tm-α (100 mg/kg) was administered 1 h after lps/galn administration. survival rates were evaluated for 24 h after lps/galn administration. plasma and liver samples were evaluated 1,3,and 7 h after lps/galn administration. survival rates were significantly higher in the tm-α-treated group than in the placebo group. a significant augmentation of plasma high-mobility group box 1 protein (hmgb1) was observed 7 h after lps/galn administration. in the tm-α-treated mice,plasma hmgb1 was significantly lower than in the placebo group. a significant augmentation of hepatic nuclear factor (nf)-κb p65 was observed in the placebo-treated group,whereas a significant reduction,relative to placebo,was observed in the tm-α-treated group. hepatic expression of tumor necrosis factor (tnf)-α and myeloperoxidase were significantly increased in the placebo group,and were similarly significantly attenuated in the tm-α-treated group. tm-α treatment also produced a significant attenuation of liver neutrophil accumulation after lps/galn administration. thus,tm-α may become a useful treatment strategy for reducing the symptoms of alf via the attenuation of lps/galn-induced hmgb1 levels. © 2015 japanese pharmacological society. production and hosting by elsevier b.v.