PMID- 21339743
OWN - NLM
STAT- MEDLINE
DCOM- 20110629
LR  - 20230216
IS  - 1530-0307 (Electronic)
IS  - 0023-6837 (Linking)
VI  - 91
IP  - 5
DP  - 2011 May
TI  - An orally available small imidazolium salt ameliorates inflammation and fibrosis 
      in a murine model of cholestasis.
PG  - 752-63
LID - 10.1038/labinvest.2011.11 [doi]
AB  - Hepatic fibrosis is the result of chronic liver injuries underlined by diverse 
      etiologies. The massive accumulation of extracellular matrix (ECM) proteins 
      during fibrogenesis leads to structural distortion and functional disruption of 
      the liver. There is currently no effective standard treatment for liver fibrosis. 
      We previously identified a class of imidazolium salts (IMSs) with anti-fibrotic 
      properties in a cell-based screen. In this report, we investigated the 
      anti-fibrotic efficacy and mechanisms of a small IMS, 1,3-diisopropylimidazolium 
      tetrafluoroborate (DPIM), in a hepatic fibrosis model induced by bile duct 
      ligation (BDL) in mice. The orally available DPIM was administered to BDL mice 
      via drinking water at three concentrations (0.5, 0.75, and 1 g/l) for 4 weeks. We 
      observed a significant reduction in inflammation and collagen deposition in the 
      liver, which could be mediated by a reduction in the expression of monocyte 
      chemoattractant protein-1 (MCP-1) and by an enhancement in the matrix 
      metalloproteinase-mediated ECM remodeling. The current findings highlight the 
      importance for simultaneously targeting multiple pathways to more effectively 
      attenuate and resolve liver fibrosis and warrant further studies on this compound 
      in additional models of hepatic fibrosis.
FAU - Ding, Zhaobing
AU  - Ding Z
AD  - Institute of Bioengineering and Nanotechnology, The Nanos, Singapore.
FAU - Kng, Yinling
AU  - Kng Y
FAU - Yang, Henry
AU  - Yang H
FAU - Ke, Zhiyuan
AU  - Ke Z
FAU - Zhuo, Lang
AU  - Zhuo L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110221
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (1,3-diisopropylimidazolium tetrafluoroborate)
RN  - 0 (Imidazoles)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 9007-34-5 (Collagen)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - Cell Line
MH  - Cholestasis/*drug therapy
MH  - Collagen/metabolism
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Fibrosis/*drug therapy
MH  - Imidazoles/administration & dosage/*therapeutic use
MH  - Immunohistochemistry
MH  - In Situ Nick-End Labeling
MH  - Inflammation/*drug therapy
MH  - Male
MH  - Matrix Metalloproteinases/metabolism
MH  - Mice
MH  - Polymerase Chain Reaction
MH  - Tissue Inhibitor of Metalloproteinase-1/metabolism
EDAT- 2011/02/23 06:00
MHDA- 2011/06/30 06:00
CRDT- 2011/02/23 06:00
PHST- 2011/02/23 06:00 [entrez]
PHST- 2011/02/23 06:00 [pubmed]
PHST- 2011/06/30 06:00 [medline]
AID - S0023-6837(22)02789-1 [pii]
AID - 10.1038/labinvest.2011.11 [doi]
PST - ppublish
SO  - Lab Invest. 2011 May;91(5):752-63. doi: 10.1038/labinvest.2011.11. Epub 2011 Feb 
      21.