PMID- 16626762
OWN - NLM
STAT- MEDLINE
DCOM- 20060818
LR  - 20161124
IS  - 0024-3205 (Print)
IS  - 0024-3205 (Linking)
VI  - 79
IP  - 9
DP  - 2006 Jul 24
TI  - Y-40138, a multiple cytokine production modulator, protects against 
      D-galactosamine and lipopolysaccharide-induced hepatitis.
PG  - 822-7
AB  - 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. This compound is 
      expected to be a new candidate for treatment of cytokine and/or chemokine-related 
      liver diseases such as alcoholic hepatitis.
FAU - Fukuda, Tetsuko
AU  - Fukuda T
AD  - Marketing and Planning Department, Sales and Marketing Division, Mitsubishi 
      Pharma Corporation, 2-5-6 Awaji-machi, Chuo-ku, Osaka 541-0047, Japan. 
      Fukada.Tetsuko@mf.m-pharma.co.jp
FAU - Mogami, Akira
AU  - Mogami A
FAU - Tanaka, Hideki
AU  - Tanaka H
FAU - Yoshikawa, Tsutomu
AU  - Yoshikawa T
FAU - Hisadome, Masao
AU  - Hisadome M
FAU - Komatsu, Hirotsugu
AU  - Komatsu H
LA  - eng
PT  - Journal Article
DEP - 20060328
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Acetamides)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Piperazines)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Y 39041)
RN  - 7535-00-4 (Galactosamine)
RN  - EC 2.6.1.2 (Alanine Transaminase)
SB  - IM
MH  - Acetamides/*pharmacology
MH  - Alanine Transaminase/blood
MH  - Animals
MH  - Cell Death/drug effects
MH  - Chemical and Drug Induced Liver Injury/pathology/*prevention & control
MH  - Chemokine CCL2/biosynthesis
MH  - Chemokines/biosynthesis
MH  - Coculture Techniques
MH  - Cytokines/*biosynthesis/blood
MH  - Female
MH  - Galactosamine/*antagonists & inhibitors/*toxicity
MH  - Hepatocytes/pathology
MH  - Lipopolysaccharides/*antagonists & inhibitors/*toxicity
MH  - Liver/pathology
MH  - Macrophages/drug effects/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Piperazines/*pharmacology
MH  - T-Lymphocytes/drug effects/metabolism
MH  - Tumor Necrosis Factor-alpha/biosynthesis
EDAT- 2006/04/22 09:00
MHDA- 2006/08/19 09:00
CRDT- 2006/04/22 09:00
PHST- 2005/08/29 00:00 [received]
PHST- 2006/01/17 00:00 [revised]
PHST- 2006/03/06 00:00 [accepted]
PHST- 2006/04/22 09:00 [pubmed]
PHST- 2006/08/19 09:00 [medline]
PHST- 2006/04/22 09:00 [entrez]
AID - S0024-3205(06)00219-0 [pii]
AID - 10.1016/j.lfs.2006.03.025 [doi]
PST - ppublish
SO  - Life Sci. 2006 Jul 24;79(9):822-7. doi: 10.1016/j.lfs.2006.03.025. Epub 2006 Mar 
      28.