PMID- 20880187
OWN - NLM
STAT- MEDLINE
DCOM- 20110310
LR  - 20131121
IS  - 1440-1681 (Electronic)
IS  - 0305-1870 (Linking)
VI  - 37
IP  - 12
DP  - 2010 Dec
TI  - Effect of indole-3-carbinol on ethanol-induced liver injury and 
      acetaldehyde-stimulated hepatic stellate cells activation using precision-cut rat 
      liver slices.
PG  - 1107-13
LID - 10.1111/j.1440-1681.2010.05450.x [doi]
AB  - 1. Indole-3-carbinol (I3C), a major indole compound found in high levels in 
      cruciferous vegetables, shows a broad spectrum of biological activities. However, 
      few studies have reported the effect of I3C on alcoholic liver injury. In the 
      present study, we investigated the protective effect of I3C on acute 
      ethanol-induced hepatotoxicity and acetaldehyde-stimulated hepatic stellate cells 
      (HSC) activation using precision-cut liver slices (PCLS). 2. Rat PCLS were 
      incubated with 50 mmol/L ethanol or 350 mumol/L acetaldehyde, and different 
      concentrations (100-400 mumol/L) of I3C were added into the culture system of 
      these two liver injury models, respectively. Hepatotoxicity was assessed by 
      measuring enzyme leakage and malondialdehyde (MDA) content in tissue. Activities 
      of alcoholic enzymes were also determined. alpha-Smooth muscle actin (alpha-SMA), 
      transforming growth factor (TGF-beta(1) ) and hydroxyproline (HYP) were used as 
      indices to evaluate the activation of HSC. In addition, matrix 
      metalloproteinase-1 (MMP-1) and the tissue inhibitor of metalloproteinase 
      (TIMP-1) were observed to estimate collagen degradation. 3. I3C significantly 
      reduced the enzyme leakage in ethanol-treated slices. In I3C groups, cytochrome 
      P450 (CYP) 2E1 activities were inhibited by 40.9-51.8%, whereas alcohol 
      dehydrogenase (ADH) activity was enhanced 1.6-fold compared with the 
      ethanol-treated group. I3C also showed an inhibitory effect against HSC 
      activation and collagen production stimulated by acetaldehyde. After being 
      incubated with I3C (400 mumol/L), the expression of MMP-1 was markedly enhanced, 
      whereas TIMP-1 was decreased. 4. These results showed that I3C protected PCLS 
      against alcoholic liver injury, which might be associated with the regulation of 
      ethanol metabolic enzymes, attenuation of oxidative injury and acceleration of 
      collagen degradation.
CI  - (c) 2010 The Authors. Clinical and Experimental Pharmacology and Physiology (c) 2010 
      Blackwell Publishing Asia Pty Ltd.
FAU - Guo, Yu
AU  - Guo Y
AD  - Department of Pharmacology, School of Basic Medical Science, Wuhan University, 
      Wuhan, China.
FAU - Wu, Xiao-Qian
AU  - Wu XQ
FAU - Zhang, Chun
AU  - Zhang C
FAU - Liao, Zhang-Xiu
AU  - Liao ZX
FAU - Wu, Yong
AU  - Wu Y
FAU - Xia, Zheng-Yuan
AU  - Xia ZY
FAU - Wang, Hui
AU  - Wang H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Australia
TA  - Clin Exp Pharmacol Physiol
JT  - Clinical and experimental pharmacology & physiology
JID - 0425076
RN  - 0 (Actins)
RN  - 0 (Indoles)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (smooth muscle actin, rat)
RN  - 3K9958V90M (Ethanol)
RN  - 9007-34-5 (Collagen)
RN  - C11E72455F (indole-3-carbinol)
RN  - EC 3.4.24.7 (Matrix Metalloproteinase 1)
RN  - GO1N1ZPR3B (Acetaldehyde)
SB  - IM
CIN - Clin Exp Pharmacol Physiol. 2012 Jul;39(7):642. PMID: 22738366
MH  - Acetaldehyde/*pharmacology
MH  - Actins/biosynthesis
MH  - Animals
MH  - Brassica/chemistry
MH  - Cell Survival/drug effects
MH  - Collagen/biosynthesis/metabolism
MH  - Ethanol/*administration & dosage
MH  - Hepatic Stellate Cells/*drug effects/metabolism
MH  - Indoles/*pharmacology
MH  - Lipid Peroxidation/drug effects
MH  - Liver/*drug effects/enzymology/metabolism/pathology
MH  - Liver Diseases, Alcoholic/enzymology/metabolism/pathology/*prevention & control
MH  - Male
MH  - Matrix Metalloproteinase 1/biosynthesis
MH  - Rats
MH  - Rats, Wistar
MH  - Specific Pathogen-Free Organisms
MH  - Tissue Inhibitor of Metalloproteinase-1/biosynthesis
MH  - Transforming Growth Factor beta1/biosynthesis/metabolism
EDAT- 2010/10/01 06:00
MHDA- 2011/03/11 06:00
CRDT- 2010/10/01 06:00
PHST- 2010/10/01 06:00 [entrez]
PHST- 2010/10/01 06:00 [pubmed]
PHST- 2011/03/11 06:00 [medline]
AID - 10.1111/j.1440-1681.2010.05450.x [doi]
PST - ppublish
SO  - Clin Exp Pharmacol Physiol. 2010 Dec;37(12):1107-13. doi: 
      10.1111/j.1440-1681.2010.05450.x.