James Karma D, Forester Sarah C, Lambert Joshua D
Department of Food Science, The Pennsylvania State University, University Park, PA 16802, USA.
Department of Food Science, The Pennsylvania State University, University Park, PA 16802, USA; Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA 16802, USA.
Food Chem Toxicol. 2015 Feb;76:103-8. doi: 10.1016/j.fct.2014.12.009. Epub 2014 Dec 17.
Human case-studies have reported an association between green tea-based dietary supplements and hepatotoxicity. Studies have demonstrated the hepatotoxicity of high-dose oral bolus dosing with the tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) in mice and dogs. We examined the effect of pretreatment with dietary EGCG on the hepatotoxicity and bioavailability of acute oral bolus dosing with EGCG in CF-1 mice. EGCG (750 mg/kg, i.g., once daily for 3 days) increased plasma alanine aminotransferase by 80-fold, decreased both reduced (by 59%) and total (by 33%) hepatic glutathione, and increased hepatic levels of phosphorylated histone 2AX. Pretreatment with dietary EGCG (3.2 mg/g diet) for 2 weeks mitigated hepatotoxicity. Acute oral EGCG also decreased mRNA expression of glutathione reductase. Dietary pretreatment prevented these decreased and increased glutathione peroxidase (Gpx)2, Gpx3, Gpx5, and Gpx7 expression. We found that dietary EGCG reduced the plasma (57% reduction) and hepatic (71% reduction) EGCG exposure following oral bolus dosing compared to mice that were not pre-treated. Overall, it appears that EGCG can modulate its own bioavailability and that dietary treatment may reduce the toxic potential of acute high oral bolus doses of EGCG. These data may partly explain the observed variation in hepatotoxic response to green tea-containing dietary supplements.
人体案例研究报告了绿茶类膳食补充剂与肝毒性之间的关联。研究已证明，小鼠和犬经口大剂量推注给予茶多酚（-）-表没食子儿茶素-3-没食子酸酯（EGCG）具有肝毒性。我们研究了在CF-1小鼠中，经膳食给予EGCG预处理对急性经口推注给予EGCG所致肝毒性和生物利用度的影响。EGCG（750mg/kg，灌胃，每日1次，共3天）使血浆丙氨酸转氨酶升高80倍，使肝脏还原型谷胱甘肽（降低59%）和总谷胱甘肽（降低33%）均减少，并使肝脏磷酸化组蛋白2AX水平升高。经膳食给予EGCG（3.2mg/g饲料）预处理2周可减轻肝毒性。急性经口给予EGCG还可降低谷胱甘肽还原酶的mRNA表达。膳食预处理可防止谷胱甘肽过氧化物酶（Gpx）2、Gpx3、Gpx5和Gpx7表达的这些降低和升高。我们发现，与未预处理的小鼠相比，经膳食给予EGCG预处理的小鼠经口推注给药后，血浆（降低57%）和肝脏（降低71%）中EGCG的暴露量减少。总体而言，EGCG似乎可以调节其自身的生物利用度，膳食处理可能会降低急性经口大剂量给予EGCG的潜在毒性。这些数据可能部分解释了观察到的对含绿茶膳食补充剂肝毒性反应的差异。
