Literature DB >> 17072764

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 Miyaso1, Yoshinori Morimoto, Michitaka Ozaki, Sanae Haga, Susumu Shinoura, Yasuhiro Choda, Hiroshi Murata, Goutaro Katsuno, Kamul Huda, Hideo Takahashi, Noriaki Tanaka, Hiromi Iwagaki.   

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-alpha, IL-1beta, and IFN-gamma 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-alpha, IL-1beta, and IFN-gammaproduction in liver.

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Year:  2006        PMID: 17072764     DOI: 10.1007/s10620-006-9141-1

Source DB:  PubMed          Journal:  Dig Dis Sci        ISSN: 0163-2116            Impact factor:   3.199


  42 in total

1.  A Toll-like receptor recognizes bacterial DNA.

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Journal:  Nature       Date:  2000-12-07       Impact factor: 49.962

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Journal:  Immunol Today       Date:  2000-05

Review 3.  Toll-like receptors in the induction of the innate immune response.

Authors:  A Aderem; R J Ulevitch
Journal:  Nature       Date:  2000-08-17       Impact factor: 49.962

4.  Effects of nafamostat mesilate, a synthetic protease inhibitor, on immunity and coagulation after hepatic resection.

Authors:  H Inagaki; T Nonami; T Kurokawa; Y Takeuchi; N Okuda; A Nakao; J Sakamoto
Journal:  Hepatogastroenterology       Date:  1999 Nov-Dec

5.  FUT-175 inhibits the production of IL-6 and IL-8 in human monocytes.

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Journal:  Res Commun Mol Pathol Pharmacol       Date:  1999-01

6.  Granulocyte proteases and hydrogen peroxide synergistically inactivate thrombomodulin of endothelial cells in vitro.

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Journal:  J Lab Clin Med       Date:  1994-06

7.  The role of bile acids in the development of endotoxemia during obstructive jaundice in the rat.

Authors:  H Van Bossuyt; C Desmaretz; G B Gaeta; E Wisse
Journal:  J Hepatol       Date:  1990-05       Impact factor: 25.083

8.  Heterotrimeric G proteins physically associated with the lipopolysaccharide receptor CD14 modulate both in vivo and in vitro responses to lipopolysaccharide.

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Journal:  J Clin Invest       Date:  1998-12-01       Impact factor: 14.808

9.  Failure of the gut barrier system enhances liver injury in rats: protection of hepatocytes by gut-derived hepatocyte growth factor.

Authors:  Yasuhiro Choda; Yoshinori Morimoto; Hideaki Miyaso; Susumu Shinoura; Shinya Saito; Takahito Yagi; Hiromi Iwagaki; Noriaki Tanaka
Journal:  Eur J Gastroenterol Hepatol       Date:  2004-10       Impact factor: 2.566

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Authors:  P C Sedman; J Macfie; P Sagar; C J Mitchell; J May; B Mancey-Jones; D Johnstone
Journal:  Gastroenterology       Date:  1994-09       Impact factor: 22.682

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  6 in total

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2.  Betaine inhibits toll-like receptor 4 expression in rats with ethanol-induced liver injury.

Authors:  Qing-Zhao Shi; Lu-Wen Wang; Wei Zhang; Zuo-Jiong Gong
Journal:  World J Gastroenterol       Date:  2010-02-21       Impact factor: 5.742

3.  Heme oxygenase-1 protects donor livers from ischemia/reperfusion injury: the role of Kupffer cells.

Authors:  Zhong Zeng; Han-Fei Huang; Ming-Qing Chen; Fei Song; Yu-Jun Zhang
Journal:  World J Gastroenterol       Date:  2010-03-14       Impact factor: 5.742

4.  Identification and confirmation of biomarkers using an integrated platform for quantitative analysis of glycoproteins and their glycosylations.

Authors:  Yashu Liu; Jintang He; Chen Li; Ricardo Benitez; Sherry Fu; Jorge Marrero; David M Lubman
Journal:  J Proteome Res       Date:  2010-02-05       Impact factor: 4.466

5.  Nafamostat prevents hypothermia and improves survival time after administration of lipopolysaccharide in a mouse surgical model.

Authors:  Yushi U Adachi; Yukako Obata; Katsumi Suzuki; Hiromi Katoh; Taiga Itagaki; Matsuyuki Doi; Shigehito Sato
Journal:  J Anesth       Date:  2009-11-18       Impact factor: 2.078

6.  The modulation of TRPM7 currents by nafamostat mesilate depends directly upon extracellular concentrations of divalent cations.

Authors:  Xuanmao Chen; Tomohiro Numata; Minghua Li; Yasuo Mori; Beverley A Orser; Michael F Jackson; Zhi-Gang Xiong; John F MacDonald
Journal:  Mol Brain       Date:  2010-12-01       Impact factor: 4.041

  6 in total

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