Hepatotoxicity of high oral dose (-)-epigallocatechin-3-gallate in mice

Joshua D. Lambert, Mary J. Kennett, Shengmin Sang, Kenneth R. Reuhl, Jihyeung Ju, Chung S. Yang

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Abstract

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 γ-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.

Original languageEnglish (US)
Pages (from-to)409-416
Number of pages8
JournalFood and Chemical Toxicology
Volume48
Issue number1
DOIs
StatePublished - Jan 1 2010

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hepatotoxicity
epigallocatechin
mouth
mice
dosage
Tea
Plasmas
Dietary supplements
tea (beverage)
8-epi-prostaglandin F2alpha
Liver
green tea
Dietary Supplements
Alanine Transaminase
alanine transaminase
liver
dietary supplements
epigallocatechin gallate
Oxidative stress
Beverages

All Science Journal Classification (ASJC) codes

  • Food Science
  • Toxicology

Cite this

Lambert, Joshua D. ; Kennett, Mary J. ; Sang, Shengmin ; Reuhl, Kenneth R. ; Ju, Jihyeung ; Yang, Chung S. / Hepatotoxicity of high oral dose (-)-epigallocatechin-3-gallate in mice. In: Food and Chemical Toxicology. 2010 ; Vol. 48, No. 1. pp. 409-416.
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Hepatotoxicity of high oral dose (-)-epigallocatechin-3-gallate in mice. / Lambert, Joshua D.; Kennett, Mary J.; Sang, Shengmin; Reuhl, Kenneth R.; Ju, Jihyeung; Yang, Chung S.

In: Food and Chemical Toxicology, Vol. 48, No. 1, 01.01.2010, p. 409-416.

Research output: Contribution to journalArticle

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