A metabonomic characterization of (+)-usnic acid-induced liver injury by gas chromatography-mass spectrometry-based metabolic profiling of the plasma and liver in rat

Xiaoyan Lu, Qinqin Zhao, Yu Tian, Shun Xiao, Tingting Jin, Xiaohui Fan

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22 Scopus citations

Abstract

Three doses of (+)-usnic acid (100, 200, and 240 mg/kg per d) were administered orally to Wistar rats for 8 days, and metabonomic characterization of (+)-usnic acid-induced liver injury based on gas chromatography-mass spectrometry metabolic profiles was evaluated. Serum biochemical analysis and histopathological examinations were simultaneously performed. The liver/body weight ratio was significantly increased in (+)-usnic acid-treated groups, whereas serum alanine aminotransferase and total bilirubin were significantly elevated. In liver sections of 200 and 240 mg/kg dosage groups, widespread hydropic degeneration of hepatocytes was observed. Clusters in partial least squares discriminant analysis score plots showed control and (+)-usnic acid-treated groups had an obvious separation. (+)-Usnic acid exposure can lead to disturbances in energy metabolism, amino acid metabolism, lipid metabolism, and nucleotide metabolism, which may be attributable to (+)-usnic acid toxicological effects on the liver through oxidative stress. The significant changes in 22 metabolites in liver might be adopted as potential biomarkers.

Original languageEnglish (US)
Pages (from-to)478-491
Number of pages14
JournalInternational Journal of Toxicology
Volume30
Issue number5
DOIs
StatePublished - Oct 2011

Keywords

  • gas chromatography-mass spectrometry
  • liver injury
  • metabonomics
  • partial least squares discriminant analysis
  • usnic acid

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