Document Detail


Hepatotoxicity of high oral dose (-)-epigallocatechin-3-gallate in mice.
MedLine Citation:
PMID:  19883714     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) has been studied for chronic disease preventive effects, and is marketed as part of many dietary supplements. However, case-reports have associated the use of green tea-based supplements with liver toxicity. We studied the hepatotoxic effects of high dose EGCG in male CF-1 mice. A single dose of EGCG (1500 mg/kg, i.g.) increased plasma alanine aminotransferase (ALT) by 138-fold and reduced survival by 85%. Once-daily dosing with EGCG increased hepatotoxic response. Plasma ALT levels were increased 184-fold following two once-daily doses of 750 mg/kg, i.g. EGCG. Moderate to severe hepatic necrosis was observed following treatment with EGCG. EGCG hepatotoxicity was associated with oxidative stress including increased hepatic lipid peroxidation (5-fold increase), plasma 8-isoprostane (9.5-fold increase) and increased hepatic metallothionein and gamma-histone 2AX protein expression. EGCG also increased plasma interleukin-6 and monocyte chemoattractant protein-1. Our results indicate that higher bolus doses of EGCG are hepatotoxic to mice. Further studies on the dose-dependent hepatotoxic effects of EGCG and the underlying mechanisms are important given the increasing use of green tea dietary supplements, which may deliver much higher plasma and tissue concentrations of EGCG than tea beverages.
Authors:
Joshua D Lambert; Mary J Kennett; Shengmin Sang; Kenneth R Reuhl; Jihyeung Ju; Chung S Yang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-10-31
Journal Detail:
Title:  Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association     Volume:  48     ISSN:  1873-6351     ISO Abbreviation:  Food Chem. Toxicol.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-02-01     Completed Date:  2010-04-15     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  8207483     Medline TA:  Food Chem Toxicol     Country:  England    
Other Details:
Languages:  eng     Pagination:  409-16     Citation Subset:  IM    
Copyright Information:
Copyright 2009 Elsevier Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Aldehydes / pharmacology
Animals
Antioxidants / pharmacokinetics,  toxicity*
Biological Markers
Catechin / analogs & derivatives*,  pharmacokinetics,  toxicity
Chromatography, High Pressure Liquid
Cysteine / urine
Cytokines / metabolism
Dose-Response Relationship, Drug
Drug-Induced Liver Injury / pathology*
Immunohistochemistry
Lipid Peroxidation / drug effects
Liver Function Tests
Male
Metallothionein / metabolism
Mice
Oxidants / toxicity
Oxidative Stress / drug effects
Spectrometry, Mass, Electrospray Ionization
Survival Analysis
Grant Support
ID/Acronym/Agency:
CA125780/CA/NCI NIH HHS; CA88961/CA/NCI NIH HHS; E05022//PHS HHS; P01 CA088961/CA/NCI NIH HHS; P01 CA088961-05/CA/NCI NIH HHS; P30 ES005022/ES/NIEHS NIH HHS; P30 ES005022-109003/ES/NIEHS NIH HHS; R01 AT004678/AT/NCCAM NIH HHS; R03 CA125780/CA/NCI NIH HHS; R03 CA125780-03/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Aldehydes; 0/Antioxidants; 0/Biological Markers; 0/Cytokines; 0/Oxidants; 29343-52-0/4-hydroxy-2-nonenal; 8R1V1STN48/Catechin; 9038-94-2/Metallothionein; BQM438CTEL/epigallocatechin gallate; K848JZ4886/Cysteine
Comments/Corrections

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