Abstract
Acute and fulminant liver failure induced by viral hepatitis, alcohol or other hepatotoxic drugs are associated with tumor necrosis factor (TNF) production. D-Galactosamine (D-GalN) and lipopolysaccharide (LPS)-induced liver injury is an experimental model of fulminant hepatic failure. In this model, TNF-alpha plays a central role in the pathogenesis of D-GalN/LPS-induced liver injury in mice. Y-40138, N-[1-(4-[4-(pyrimidin-2-yl)piperazin-1-yl]methyl phenyl)cyclopropyl] acetamide.HCl inhibits TNF-alpha and augments interleukin (IL)-10 production in LPS-injected mice in plasma. In the present study, we examined the effect of Y-40138 on D-GalN/LPS-induced hepatitis. Y-40138 (10mg/kg, i.v.) significantly suppressed TNF-alpha and monocyte chemoattractant protein-1 (MCP-1) production and augmented IL-10 production in plasma. In addition, Y-40138 significantly inhibited TNF-alpha production induced by direct interaction between human T lymphocytes and macrophages. Y-40138 suppressed plasma alanine transaminase (ALT) elevation and improved survival rate in D-GalN/LPS-injected mice, and it is suggested that the protective effect of Y-40138 on hepatitis may be mediated by inhibition of TNF-alpha and MCP-1, and/or augmentation of IL-10. ...Continue Reading
References
Aug 1, 1991·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·C J McClain
Mar 1, 1991·Journal of Hepatology·N SheronR Williams
Jun 15, 1990·Annals of Internal Medicine·G L BirdR S Williams
Mar 1, 1995·Shock·W G JungerG Schlag
Nov 1, 1994·Journal of Hepatology·G Tiegs
Dec 1, 1993·The Journal of Experimental Medicine·M A CassatellaG Constantin
Jan 1, 1993·Annual Review of Immunology·K W MooreT R Mosmann
Feb 1, 1993·The Journal of Experimental Medicine·C GérardT Velu
Sep 1, 1996·Gastroenterology·L SantucciA Morelli
Mar 1, 1997·Gastroenterology·H LouisJ Devière
Jul 7, 1997·The Journal of Experimental Medicine·J H GongI Clark-Lewis
Feb 12, 1998·The New England Journal of Medicine·A D Luster
Aug 14, 1999·Gut·N C FisherD H Adams
Feb 11, 2000·The Journal of Infectious Diseases·D P OlszynaT van Der Poll
Mar 24, 2000·European Journal of Pharmacology·T FukudaM Hisadome
Mar 21, 2001·The Journal of Experimental Medicine·D R HuangR M Ransohoff
Mar 1, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Maria B ArveloChristiane Ferran
Apr 22, 2004·Journal of Ethnopharmacology·Ji-Xing NanJung-Joon Lee
Citations
Aug 24, 2007·Clinical and Experimental Pharmacology & Physiology·Herman ChanMichael S-C Tam
Jan 22, 2011·Journal of Gastroenterology and Hepatology·Hideto KawarataniHiroshi Fukui
Nov 10, 2011·PloS One·Shihui SunYusen Zhou
Jun 12, 2013·PloS One·Dong-yu LiangYan-yan Wang
Feb 6, 2009·Archives of Histology and Cytology·Tadayuki IkedaTetsuji Sato
Nov 26, 2009·World Journal of Gastroenterology : WJG·Tatsuhiro TsujimotoHiroshi Fukui
Apr 16, 2013·Biochemical and Biophysical Research Communications·Xiao LiuJiong Li
Sep 11, 2007·European Journal of Pharmacology·Tsuyoshi YoshidaHideo Inoue
Apr 25, 2007·Experimental Cell Research·Hye Young KimJaehun Cheong
Dec 31, 2009·European Journal of Clinical Investigation·L-M LiuJ Luo
Feb 11, 2015·Experimental and Therapeutic Medicine·Wei-Ting QinBing-Wei Sun
Mar 25, 2015·PloS One·Liang Ming LiuTong Zhu
Nov 16, 2007·Shock·Takeshi HijikawaTadayoshi Okumura
May 11, 2019·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Xiao WangWanyu Shi
Jan 13, 2012·The Journal of Pharmacology and Experimental Therapeutics·Chongyang DengLijuan Chen
Jul 6, 2017·Molecular Medicine Reports·Xiao-Juan ChenQi-Ping Lu
Mar 26, 2015·World Journal of Gastroenterology : WJG·Liang-Ming LiuTong Zhu
Mar 27, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Qihui LuoZhengli Chen
Dec 26, 2018·International Immunopharmacology·Zuochuan DingPing Zhou