Protective effects of nafamostat mesilate on liver injury induced by lipopolysaccharide in rats: Possible involvement of CD14 and TLR-4 downregulation on Kupffer cells

Hideaki Miyaso, Yoshinori Morimoto, Michitaka Ozaki, Sanae Haga, Susumu Shinoura, Yasuhiro Choda, Hiroshi Murata, Goutaro Katsuno, Kamul Huda, Hideo Takahashi, Noriaki Tanaka, Hiromi Iwagaki

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Nafamostat mesilate (NM) is a synthetic protease inhibitor with various biological effects. To determine its effect on liver injury related to sepsis, we investigated the effects of NM on lipopolysaccharide (LPS)-induced liver injury. Wistar rats were allocated into two groups; the NM group underwent intraperitoneal NM administration 30 min before LPS administration, and the control group underwent PBS administration. Serum AST and ALT levels were significantly decreased in NM-treated rats. Reduced levels of TNF-α, IL-1β, and IFN-γ were observed after LPS administration in NM-treated rats. No significant differences were observed in IL-6 levels between the NM and the control group. In contrast, HGF levels were significantly increased only in control rats. NM treatment decreased protein and mRNA levels of TLR-4 and CD14. Our data suggest that NM treatment has protective effects against LPS-induced hepatotoxicity through downregulation of TLR4 and CD14 in liver, which decreased TNF-α, IL-1β, and IFN-γproduction in liver.

Original languageEnglish
Pages (from-to)2007-2012
Number of pages6
JournalDigestive Diseases and Sciences
Volume51
Issue number11
DOIs
Publication statusPublished - Nov 2006

Keywords

  • CD14
  • Lipopolysaccharide
  • Liver injury
  • Nafamostat mesilate
  • TLR-4

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

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