Antioxidant and hepato-preventive effect of Citrus aurantium extract against carbon tetrachloride-induced hepatotoxicity in rats and characterisation of its bioactive compounds by HPLC-MS

Arch Physiol Biochem. 2019 Oct;125(4):332-343. doi: 10.1080/13813455.2018.1461233. Epub 2018 Apr 17.


The objective of this study is to explore the preventive effects of ethyl acetate fraction from Citrus aurantium leaf extract (EACA), associated with its phytochemical content, against the toxic impacts of acute exposure to carbon tetrachloride (CCl4) in the liver of adult rats. HPLC analysis of ethyl acetate fraction from extract C. aurantium revealed eight compounds. Administration of a single dose of CCl4 caused hepatoxicity as monitored by an increase in lipid peroxidation (thiobarbituric acid reactive substances) and in protein carbonyl level but a decrease in antioxidant markers in the liver tissue. The pre-treatment with EACA; significantly prevented the increased plasma levels of hepatic markers and lipid levels induced by CCl4 in rats. Furthermore, this fraction ameliorated biochemical and histological parameters as compared to CCl4-treated group. Our results suggest that C. aurantium contains promising substances to counteract the CCl4 intoxication and can be efficient in the prevention of hepatotoxicity complications.

Keywords: Carbon tetrachloride;; HPLC-MS; extract fractionation; hepato-preventive; oxidative stress; phytochemical; rats.

MeSH terms

  • Acetates / analysis
  • Alkaline Phosphatase / metabolism
  • Animals
  • Antioxidants / chemistry*
  • Antioxidants / pharmacology*
  • Carbon Tetrachloride / toxicity*
  • Chromatography, High Pressure Liquid
  • Citrus / chemistry*
  • L-Lactate Dehydrogenase / metabolism
  • Lipid Peroxidation / drug effects
  • Liver / cytology
  • Liver / drug effects*
  • Liver / metabolism
  • Mass Spectrometry
  • Oxidative Stress / drug effects
  • Phenols / analysis
  • Plant Extracts / chemistry*
  • Plant Extracts / pharmacology*
  • Rats


  • Acetates
  • Antioxidants
  • Phenols
  • Plant Extracts
  • ethyl acetate
  • Carbon Tetrachloride
  • L-Lactate Dehydrogenase
  • Alkaline Phosphatase