Extract of Triticum aestivum Sprouts Suppresses Acetaminophen-Induced Hepatotoxicity in Mice by Inhibiting Oxidative Stress

Molecules. 2021 Oct 20;26(21):6336. doi: 10.3390/molecules26216336.

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.

Keywords: Triticum aestivum sprouts; acetaminophen; apoptosis; hepatotoxicity; oxidative stress.

MeSH terms

  • Acetaminophen / adverse effects
  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects
  • Biomarkers
  • Chemical and Drug Induced Liver Injury / drug therapy
  • Chemical and Drug Induced Liver Injury / etiology*
  • Chemical and Drug Induced Liver Injury / metabolism*
  • Chemical and Drug Induced Liver Injury / prevention & control
  • Cytochrome P-450 CYP2E1 / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Liver Function Tests
  • Male
  • Mice
  • Molecular Structure
  • NF-E2-Related Factor 2
  • Oxidative Stress / drug effects*
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Protective Agents
  • Signal Transduction / drug effects
  • Triticum / chemistry*

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Biomarkers
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Plant Extracts
  • Protective Agents
  • Acetaminophen
  • Cytochrome P-450 CYP2E1