Abstract
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.
Highlights
Studies have shown that intake of green tea or green tea polyphenols (GTPs) can reduce the development and progression of various diseases such as cancer, cardiovascular disease, and neurodegenerative diseases [1,2]
Our results indicate that EGCG may reduce oxidative stress and lower the metabolism and toxicity of acetaminophen
In experiment I, we evaluated the effects of supplementation with EGCG for four weeks on oxidative stress, drug-metabolizing enzyme activities and membrane transporters in the liver of normal rats
Summary
Studies have shown that intake of green tea or green tea polyphenols (GTPs) can reduce the development and progression of various diseases such as cancer, cardiovascular disease, and neurodegenerative diseases [1,2]. The other way to lower APAP toxicity is to facilitate the excretion of glucuronate, sulfate, GSH conjugates, and oxidative stress products from the liver by increasing the expression of membrane transporters such as multidrug resistance-associated protein (Mrp)2/3 or reduced uptake transporters such as organic anion-transporting polypeptide (OATP) 1a1 and OATP 1b2 [18,19,20]. Administration of GTPs has been shown to provide protection against APAP-induced liver injury [21]. Supplementation with EGCG (0.54%, w/w) in the diet for one week had an inhibitory effect against APAP-induced liver injury in rats [22]. Rats were fed a diet containing EGCG for a longer time (four weeks) to investigate the effects of EGCG on oxidative stress, drug-metabolizing enzymes, and membrane transporters in the liver. The effects of EGCG on the metabolism and toxicity of APAP in the liver were investigated
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