| Autor: |
Wataru Osumi, Denan Jin, Yoshiro Imai, Keitaro Tashiro, Zhong-Lian Li, Yoshinori Otsuki, Kentaro Maemura, Koji Komeda, Fumitoshi Hirokawa, Michihiro Hayashi, Shinji Takai, Kazuhisa Uchiyama |
| Jazyk: |
angličtina |
| Rok vydání: |
2015 |
| Předmět: |
|
| Zdroj: |
Journal of Pharmacological Sciences, Vol 129, Iss 4, Pp 233-239 (2015) |
| Druh dokumentu: |
article |
| ISSN: |
1347-8613 |
| DOI: |
10.1016/j.jphs.2015.11.007 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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