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Open AccessArticle

Epigallocatechin-3-Gallate Reduces Hepatic Oxidative Stress and Lowers CYP-Mediated Bioactivation and Toxicity of Acetaminophen in Rats

1
Department of Nutrition, China Medical University, 91 Hsueh-shih Road, Taichung 404, Taiwan
2
Department of Nutrition, Chung Shan Medical University, 110 Sec.1, Jianguo North Road, Taichung 40201, Taiwan
*
Author to whom correspondence should be addressed.
Nutrients 2019, 11(8), 1862; https://doi.org/10.3390/nu11081862
Received: 21 July 2019 / Revised: 5 August 2019 / Accepted: 7 August 2019 / Published: 10 August 2019
(This article belongs to the Special Issue Targeted Nutrition in Chronic Disease)
Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in green tea. To investigate the effects of dietary EGCG on oxidative stress and the metabolism and toxicity of acetaminophen in the liver, rats were fed diets with (0.54%) or without EGCG supplementation for four weeks and were then injected intraperitoneally with acetaminophen (1 g/kg). The results showed that EGCG lowered hepatic oxidative stress and cytochrome P450 (CYP) 1A2, 2E1, and 3A, and UDP-glucurosyltransferase activities prior to acetaminophen injection. After acetaminophen challenge, the elevations in plasma alanine aminotransferase activity and histological changes in the liver were ameliorated by EGCG treatment. EGCG reduced acetaminophen-induced apoptosis by lowering the Bax/Bcl2 ratio in the liver. EGCG mildly increased autophagy by increasing the LC3B II/I ratio. Lower hepatic acetaminophen–glutathione and acetaminophen–protein adducts contents were observed after EGCG treatment. EGCG increased glutathione peroxidase and NAD(P)H quinone 1 oxidoreductase activities and reduced organic anion-transporting polypeptides 1a1 expression in the liver after acetaminophen treatment. Our results indicate that EGCG may reduce oxidative stress and lower the metabolism and toxicity of acetaminophen. The reductions in CYP-mediated acetaminophen bioactivation and uptake transporter, as well as enhanced antioxidant enzyme activity, may limit the accumulation of toxic products in the liver and thus lower hepatotoxicity. View Full-Text
Keywords: epigallocatechin-3-gallate; acetaminophen; cytochrome P-450; bioactivation; apoptosis; autophagy; hepatotoxicity epigallocatechin-3-gallate; acetaminophen; cytochrome P-450; bioactivation; apoptosis; autophagy; hepatotoxicity
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Yao, H.-T.; Li, C.-C.; Chang, C.-H. Epigallocatechin-3-Gallate Reduces Hepatic Oxidative Stress and Lowers CYP-Mediated Bioactivation and Toxicity of Acetaminophen in Rats. Nutrients 2019, 11, 1862.

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