title: Protective effects of nafamostat mesilate on liver injury induced by lipopolysaccharide in rats: possible involvement of CD14 and TLR-4 downregulation on Kupffer cells.
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.
authors.affiliation: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Miyaso
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Morimoto
authors.forename: Michitaka
authors.initials: M
authors.lastname: Ozaki
authors.forename: Sanae
authors.initials: S
authors.lastname: Haga
authors.forename: Susumu
authors.initials: S
authors.lastname: Shinoura
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Choda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Murata
authors.forename: Goutaro
authors.initials: G
authors.lastname: Katsuno
authors.forename: Kamul
authors.initials: K
authors.lastname: Huda
authors.forename: Hideo
authors.initials: H
authors.lastname: Takahashi
authors.forename: Noriaki
authors.initials: N
authors.lastname: Tanaka
authors.forename: Hiromi
authors.initials: H
authors.lastname: Iwagaki
mesh_terms: D000818:Animals; D001550:Benzamidines; D056486:Chemical and Drug Induced Liver Injury; D015536:Down-Regulation; D006146:Guanidines / Q000494:pharmacology / Q000627:therapeutic use*; D017228:Hepatocyte Growth Factor / Q000097:blood; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000097:blood; D007728:Kupffer Cells / Q000502:physiology*; D018950:Lipopolysaccharide Receptors / Q000502:physiology; D008107:Liver Diseases / Q000188:drug therapy*; D008297:Male; D011480:Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D051197:Toll-Like Receptor 4 / Q000502:physiology
chemical_list: D001550:Benzamidines; D006146:Guanidines; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D011480:Protease Inhibitors; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D017228:Hepatocyte Growth Factor; C032855:nafamostat