Abstract

Wheat (Triticum aestivum L.) is the oldest known food crop, and many studies have reported that wheat shoots (i.e., wheatgrass) possess anti-cancer, anti-inflammatory, and antioxidant activities. However, the potentially ameliorative effect of wheat shoots on hepatotoxicity caused by high doses of N-acetyl-para-aminophenol (acetaminophen, APAP) has yet to be reported. C57BL/6 mice received daily oral TAE (100 or 200 mg/kg), positive control (silymarin 100 mg/kg), or negative control (saline vehicle) treatments for 7 days prior to intraperitoneal APAP injection. Histological, serum (ELISA), Western blotting, and quantitative PCR analyses of excised liver tissues were then performed. Pre-treatment with TAE (100 or 200 mg/kg) ameliorated APAP-induced pathological damage (i.e., hepatotoxic lesions), reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and also ameliorated APAP-induced increases in oxidative stress, thereby inhibiting oxidative liver damage and reducing the expression of inflammatory cytokines. In addition, TAE pre-treatment inhibited the expression of Cytochrome P4502E1 (CYP2E1), which is a key enzyme in the onset of APAP-induced hepatotoxicity, suppressed the expression of the target proteins regulated by the antioxidant enzyme Nrf2, and suppressed hepatocyte apoptosis. These findings suggest that TAE is an attractive therapeutic candidate that exhibits potential hepatoprotective activity by inhibiting oxidative stress, inflammation, apoptosis, and liver damage.

Highlights

  • Acetaminophen (N-acetyl-para-aminophenol (APAP)) is a widely used pain reliever and antipyretic and is considered safe at therapeutic doses [1]

  • 4% is oxidized by cytochrome P450 (CYP450) into N-acetyl-p-benzoquinone imine (NAPQI), an intermediate metabolite [1]

  • The present study evaluated the hepatoprotective effects of TAE in mice with APAPinduced hepatotoxicity

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Summary

Introduction

Acetaminophen (N-acetyl-para-aminophenol (APAP)) is a widely used pain reliever and antipyretic and is considered safe at therapeutic doses [1]. As many people take it, drug addiction is common, and many studies have reported that death can occur as a result of liver damage and acute liver failure [1]. 4% is oxidized by cytochrome P450 (CYP450) into N-acetyl-p-benzoquinone imine (NAPQI), an intermediate metabolite [1]. The transient receptor potential ankyrin-1 (TRPA1) channel is expressed by peptidergic primary sensory neurons [2]. NAPQI is a powerful TRPA1 agonist, and the analgesic effect of APAP causes the action of metabolites of the parent drug on sensory neuron TRP channels, preventing nerve cells from transmitting information and thereby attenuating the transmission of pain signals to the brain [3]

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