Protective effects of (-)-epigallocatechin-3-gallate against acetaminophen-induced liver injury in rats).

Hsien-Tsung Yao,Hui-Ting Yang,Chen-Hui Chang,Mei-Chin Yin,Yu-Chi Yang

doi:10.7603/s40681-015-0015-8

Abstract

(-)-Epigallocatechin-3-gallate (EGCG) is the most abundant catechin with various biological activities found in tea. In this study, the effects of EGCG on the metabolism and toxicity of acetaminophen in rat liver were investigated. Male Sprague-Dawley rats were fed a controlled diet without or with EGCG (0.54 %, w/w) for 1 week and were then intraperitoneally injected with acetaminophen (1 g/kg body weight) and killed after 12 h. Concentrations of acetaminophen and its conjugates in plasma and liver were then determined. The cytochrome P450 (CYP) and phase II enzymes activities were also evaluated. Rats fed the EGCG diet had lower plasma alanine aminotransferase and aspartate aminotransferase activities, as indices of hepatotoxicity, after acetaminophen treatment. Morphological damage by acetaminophen was lower in rats fed the EGCG diet. In addition, EGCG significantly reduced hepatic activities of midazolam 1-hydroxylation (CYP3A), nitrophenol 6-hydroxylase (CYP2E1), UDP-glucurosyltransferase, and sulfotransferase. Finally, EGCG feeding reduced acetaminophen-glucuronate and acetaminophen-glutathione contents in plasma and liver. These results indicate that EGCG feeding may reduce the metabolism and toxicity of acetaminophen in rats.

Highlights

Phytochemicals are found in plant-based foods such as fruits, vegetables, beans, and grains, and they may reduce the risk of a number of chronic diseases including cancer, cardiovascular disease, and diabetes [1]
Rats fed on the 0.18% and 0.54% EGCG diets for 1 week had significantly reduced (P < 0.05) testosterone 6β-hydroxylase (CYP3A) in their livers
The results of the present study show that EGCG feeding significantly reduced the elevation of plasma ALT and AST activities that were first induced by APAP

Summary

Introduction

Phytochemicals are found in plant-based foods such as fruits, vegetables, beans, and grains, and they may reduce the risk of a number of chronic diseases including cancer, cardiovascular disease, and diabetes [1]. It is known that phytochemicals can influence the pharmacological activity of drugs and their toxicities by modifying the drug metabolism system, including drugmetabolizing enzymes and transporters [2, 3]. The initiation of APAP-induced liver injury results from the cytochrome P450 (CYP)-mediated metabolism of APAP into a reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI), which exerts its toxicity by covalently binding to cellular macromolecules such as proteins, lipids, and DNA [5]. NAPQI reacts with glutathione (GSH), leading to cellular GSH depletion and the production of reactive oxygen species in the liver. Studies have shown that natural products that decrease CYP enzyme activity, increase antioxidant enzyme activity or GSH levels may attenuate APAP-induced liver toxicity [6, 7]

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