PMID- 21497498
OWN - NLM
STAT- MEDLINE
DCOM- 20120604
LR  - 20120213
IS  - 1873-4847 (Electronic)
IS  - 0955-2863 (Linking)
VI  - 23
IP  - 3
DP  - 2012 Mar
TI  - Beneficial effect of docosahexaenoic acid on cholestatic liver injury in rats.
PG  - 252-64
LID - 10.1016/j.jnutbio.2010.11.022 [doi]
AB  - Bile duct obstruction and subsequent cholestasis are associated with 
      hepatocellular injury, cholangiocyte proliferation, stellate cell activation, 
      Kupffer cell activation, oxidative stress, inflammation and fibrosis. 
      Docosahexaenoic acid (DHA) is an essential polyunsaturated fatty acid that has 
      been shown to possess health beneficial effects, including hepatoprotection. 
      However, the molecular mechanism of DHA-mediated hepatoprotection is not fully 
      understood. In the present study, we report the protective effect of DHA on 
      cholestatic liver injury. Cholestasis was produced by bile duct ligation (BDL) in 
      male Sprague-Dawley rats for 3 weeks. Daily administration of DHA was started 2 
      weeks before injury and lasted for 5 weeks. In comparison with the control group, 
      the BDL group showed hepatic damage as evidenced by histological changes and 
      elevation in serum biochemicals, ductular reaction, fibrosis, inflammation and 
      oxidative stress. These pathophysiological changes were attenuated by chronic DHA 
      supplementation. DHA alleviated BDL-induced transforming growth factor beta-1 
      (TGF-beta1), intereukin-1beta, connective tissue growth factor and collagen 
      expression. The anti-fibrotic effect of DHA was accompanied by reductions in 
      alpha-smooth muscle actin-positive matrix-producing cells and Smad 2/3 activity 
      critical to the fibrogenic potential of TGF-beta1. DHA also attenuated BDL-induced 
      leukocyte accumulation and nuclear factor-kappaB (NF-kappaB) activation. Further studies 
      demonstrated an inhibitory effect of DHA on redox-sensitive intracellular 
      signaling molecule extracellular signal-regulated kinase (ERK). Taken together, 
      the hepatoprotective, anti-inflammatory and anti-fibrotic effects of DHA seem to 
      be multifactorial. The beneficial effects of chronic DHA supplementation are 
      associated with anti-oxidative and anti-inflammatory potential as well as 
      down-regulation of NF-kappaB and transforming growth factor beta/Smad signaling 
      probably via interference with ERK activation.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Chen, Wen-Ying
AU  - Chen WY
AD  - Department of Education and Research, Taichung Veterans General Hospital, 
      Taichung 407, Taiwan.
FAU - Lin, Shih-Yi
AU  - Lin SY
FAU - Pan, Hung-Chuan
AU  - Pan HC
FAU - Liao, Su-Lan
AU  - Liao SL
FAU - Chuang, Yu-Han
AU  - Chuang YH
FAU - Yen, Yu-Ju
AU  - Yen YJ
FAU - Lin, Szu-Yin
AU  - Lin SY
FAU - Chen, Chun-Jung
AU  - Chen CJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110415
PL  - United States
TA  - J Nutr Biochem
JT  - The Journal of nutritional biochemistry
JID - 9010081
RN  - 0 (Interleukin-1beta)
RN  - 0 (NF-kappa B)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 25167-62-8 (Docosahexaenoic Acids)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Animals
MH  - Bile Ducts/metabolism/pathology
MH  - Cholestasis/complications/*pathology
MH  - *Dietary Supplements
MH  - Docosahexaenoic Acids/*administration & dosage
MH  - Down-Regulation
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Fibrosis/drug therapy
MH  - Interleukin-1beta/metabolism
MH  - Ligation
MH  - Liver/drug effects/metabolism/pathology
MH  - Liver Diseases/complications/*pathology/surgery
MH  - Male
MH  - NF-kappa B/metabolism
MH  - Oxidative Stress/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction
MH  - Transforming Growth Factor beta1/metabolism
EDAT- 2011/04/19 06:00
MHDA- 2012/06/05 06:00
CRDT- 2011/04/19 06:00
PHST- 2010/05/14 00:00 [received]
PHST- 2010/11/09 00:00 [revised]
PHST- 2010/11/23 00:00 [accepted]
PHST- 2011/04/19 06:00 [entrez]
PHST- 2011/04/19 06:00 [pubmed]
PHST- 2012/06/05 06:00 [medline]
AID - S0955-2863(11)00025-8 [pii]
AID - 10.1016/j.jnutbio.2010.11.022 [doi]
PST - ppublish
SO  - J Nutr Biochem. 2012 Mar;23(3):252-64. doi: 10.1016/j.jnutbio.2010.11.022. Epub 
      2011 Apr 15.