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Protective Effects of Nafamostat Mesilate on Liver Injury Induced by Lipopolysaccharide in Rats: Possible Involvement of CD14 and TLR-4 Downregulation on Kupffer Cells

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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.

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Authors and Affiliations

  1. Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan e-mail: iwagaki@md.okayama-u.ac.jp

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

  2. Department of Surgery, Division of Organ Transplantation and Regenerative Medicine, Hokkaido University School of Medicine, N-15, W-7, Kita-ku, Sapporo, Hokkaido, 060-8638,, Japan

    Michitaka Ozaki & Sanae Haga

  3. Department of Pharmacology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama, 700-8558,, Japan

    Hideo Takahashi

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  1. Hideaki Miyaso
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Miyaso, H., Morimoto, Y., Ozaki, M. et al. Protective Effects of Nafamostat Mesilate on Liver Injury Induced by Lipopolysaccharide in Rats: Possible Involvement of CD14 and TLR-4 Downregulation on Kupffer Cells . Dig Dis Sci 51, 2007–2012 (2006). https://doi.org/10.1007/s10620-006-9141-1

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