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

Fingerprint

Kupffer Cells
Lipopolysaccharides
Down-Regulation
Liver
Wounds and Injuries
Interleukin-1
nafamostat
Control Groups
Protease Inhibitors
Wistar Rats
Interleukin-6
Sepsis
Messenger RNA

Keywords

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

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Protective effects of nafamostat mesilate on liver injury induced by lipopolysaccharide in rats : Possible involvement of CD14 and TLR-4 downregulation on Kupffer cells. / Miyaso, Hideaki; Morimoto, Yoshinori; Ozaki, Michitaka; Haga, Sanae; Shinoura, Susumu; Choda, Yasuhiro; Murata, Hiroshi; Katsuno, Goutaro; Huda, Kamul; Takahashi, Hideo; Tanaka, Noriaki; Iwagaki, Hiromi.

In: Digestive Diseases and Sciences, Vol. 51, No. 11, 11.2006, p. 2007-2012.

Research output: Contribution to journalArticle

Miyaso, H, Morimoto, Y, Ozaki, M, Haga, S, Shinoura, S, Choda, Y, Murata, H, Katsuno, G, Huda, K, Takahashi, H, Tanaka, N & Iwagaki, H 2006, 'Protective effects of nafamostat mesilate on liver injury induced by lipopolysaccharide in rats: Possible involvement of CD14 and TLR-4 downregulation on Kupffer cells', Digestive Diseases and Sciences, vol. 51, no. 11, pp. 2007-2012. https://doi.org/10.1007/s10620-006-9141-1
Miyaso, Hideaki ; Morimoto, Yoshinori ; Ozaki, Michitaka ; Haga, Sanae ; Shinoura, Susumu ; Choda, Yasuhiro ; Murata, Hiroshi ; Katsuno, Goutaro ; Huda, Kamul ; Takahashi, Hideo ; Tanaka, Noriaki ; Iwagaki, Hiromi. / Protective effects of nafamostat mesilate on liver injury induced by lipopolysaccharide in rats : Possible involvement of CD14 and TLR-4 downregulation on Kupffer cells. In: Digestive Diseases and Sciences. 2006 ; Vol. 51, No. 11. pp. 2007-2012.
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