Epigallocatechin 3-gallate ameliorates bile duct ligation induced liver injury in mice by modulation of mitochondrial oxidative stress and inflammation

Cholestatic liver fibrosis was achieved by bile duct ligation (BDL) in mice. Liver injury associated with BDL for 15 days included significant reactive oxygen/nitrogen species generation, liver inflammation, cell death and fibrosis. Administration of Epigallocatechin 3-Gallate (EGCG) in animals redu...

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Bibliographic Details
Published in:PloS one 2015-05, Vol.10 (5), p.e0126278-e0126278
Main Authors: Shen, Kezhen, Feng, Xiaowen, Su, Rong, Xie, Haiyang, Zhou, Lin, Zheng, Shusen
Format: Article
Language:English
Subjects:
Actin
Alcohol
Analysis
Animals
Antioxidants
Antioxidants (Nutrients)
Apoptosis
Bile
Bile ducts
Bile Ducts, Intrahepatic - drug effects
Bile Ducts, Intrahepatic - injuries
Cancer
Care and treatment
Catechin - administration & dosage
Catechin - analogs & derivatives
Catechin - pharmacology
Cell death
Cell Death - drug effects
Cholestasis - complications
Cholestasis - drug therapy
Cholestasis - etiology
Collaboration
Collagen
Complications and side effects
Connective tissue growth factor
Connective tissues
Cytokines
Cytokines - metabolism
Deoxyribonucleic acid
Disease Models, Animal
DNA
DNA fragmentation
Electron transport
Electron transport chain
Epigallocatechin gallate
Epigallocatechin-3-gallate
Ethics
Extracellular matrix
Fibroblasts
Fibronectin
Fibrosis
Gene expression
Gene Expression Regulation - drug effects
Glutathione
Glutathione peroxidase
Health aspects
Hepatic Stellate Cells - drug effects
Hepatic Stellate Cells - pathology
Hepatocytes
Hepatocytes - drug effects
Hepatology
Hospitals
Hydrogen
Hydrogen peroxide
Infectious diseases
Inflammation
Inflammation - drug therapy
Inflammation - etiology
Influence
Interleukin 1
Laboratory animals
Liver
Liver Cirrhosis - drug therapy
Liver Cirrhosis - etiology
Liver diseases
Manganese
Medical diagnosis
Medicine
Mice
Mitochondria
Mitochondria - drug effects
Mortality
Muscles
NF-kappa B - metabolism
NF-κB protein
Nitrogen
Oxidative stress
Oxidative Stress - drug effects
Oxygen
Peroxidase
Public health
Reactive nitrogen species
Reactive oxygen species
Risk factors
Rodents
Smooth muscle
Superoxide dismutase
Surgery
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Summary:Cholestatic liver fibrosis was achieved by bile duct ligation (BDL) in mice. Liver injury associated with BDL for 15 days included significant reactive oxygen/nitrogen species generation, liver inflammation, cell death and fibrosis. Administration of Epigallocatechin 3-Gallate (EGCG) in animals reduced liver fibrosis involving parenchymal cells in BDL model. EGCG attenuated BDL-induced gene expression of pro-fibrotic markers (Collagen, Fibronectin, alpha 2 smooth muscle actin or SMA and connective tissue growth factor or CTGF), mitochondrial oxidative stress, cell death marker (DNA fragmentation and PARP activity), NFκB activity and pro-inflammatory cytokines (TNFα, MIP1α, IL1β, and MIP2). EGCG also improved BDL induced damages of mitochondrial electron transport chain complexes and antioxidant defense enzymes such as glutathione peroxidase and manganese superoxide dismutase. EGCG also attenuated hydrogen peroxide induced cell death in hepatocytes in vitro and alleviate stellate cells mediated fibrosis through TIMP1, SMA, Collagen 1 and Fibronectin in vitro. In conclusion, the reactive oxygen/nitrogen species generated from mitochondria plays critical pathogenetic role in the progression of liver inflammation and fibrosis and this study indicate that EGCG might be beneficial for reducing liver inflammation and fibrosis.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0126278