Sensitivity to hepatotoxicity due to epigallocatechin gallate is affected by genetic background in diversity outbred mice

被引:71
作者
Church, Rachel J. [1 ]
Gatti, Daniel M. [2 ]
Urban, Thomas J. [3 ]
Long, Nanye [3 ]
Yang, Xi [4 ]
Shi, Qiang [4 ]
Eaddy, J. Scott [1 ]
Mosedale, Merrie [1 ]
Ballard, Shawn [5 ]
Churchill, Gary A. [2 ]
Navarro, Victor [6 ]
Watkins, Paul B. [1 ]
Threadgill, David W. [5 ]
Harrill, Alison H. [1 ]
机构
[1] Hamner UNC Inst Drug Safety Sci, Durham, NC 27709 USA
[2] Jackson Lab, Bar Harbor, ME 04609 USA
[3] Duke Univ, Durham, NC 27708 USA
[4] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA
[5] N Carolina State Univ, Raleigh, NC 27607 USA
[6] Einstein Healthcare Network, Philadelphia, PA 19141 USA
基金
美国国家科学基金会;
关键词
Green tea; Epigallocatechin gallate; Hepatotoxicity; Population variability; Herbal; Diversity outbred; INDUCED LIVER-INJURY; ACETAMINOPHEN-INDUCED HEPATOTOXICITY; GREEN TEA EXTRACT; DIETARY-SUPPLEMENTS; HYDROXYCUT; DISCOVERY; COMPLEX; TRAITS;
D O I
10.1016/j.fct.2014.11.008
中图分类号
TS2 [食品工业];
学科分类号
0832 ;
摘要
Consumer use of herbal and dietary supplements has recently grown in the United States and, with increased use, reports of rare adverse reactions have emerged. One such supplement is green tea extract, containing the polyphenol epigallocatechin gallate (EGCG), which has been shown to be hepatotoxic at high doses in animal models. The Drug-Induced Liver Injury Network has identified multiple patients who have experienced liver injury ascribed to green tea extract consumption and the relationship to dose has not been straightforward, indicating that differences in sensitivity may contribute to the adverse response in susceptible people. The Diversity Outbred (DO), a genetically heterogeneous mouse population, provides a potential platform for study of interindividual toxicity responses to green tea extract. Within the DO population, an equal exposure to EGCG (50 mg/kg; daily for three days) was found to be tolerated in the majority of mice; however, a small fraction of the animals (16%; 43/272) exhibited severe hepatotoxicity (10-86.8% liver necrosis) that is analogous to the clinical cases. The data indicate that the DO mice may provide a platform for informing risk of rare, adverse reactions that may occur in consumer populations upon ingestion of concentrated herbal products. (C) 2014 The Authors. Published by Elsevier Ltd.
引用
收藏
页码:19 / 26
页数:8
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