title: A metabonomic characterization of (+)-usnic acid-induced liver injury by gas chromatography-mass spectrometry-based metabolic profiling of the plasma and liver in rat.
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.
authors: Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, 866 YuHangTang Road, Hangzhou, 310058 People's Republic of China.
authors: Xiaoyan
authors: X
authors: Lu
authors: Qinqin
authors: Q
authors: Zhao
authors: Yu
authors: Y
authors: Tian
authors: Shun
authors: S
authors: Xiao
authors: Tingting
authors: T
authors: Jin
authors: Xiaohui
authors: X
authors: Fan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001572:Benzofurans / Q000633:toxicity*; D015415:Biomarkers; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D022781:Hepatocytes / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D018384:Oxidative Stress; D010949:Plasma / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results
chemical_list: D001572:Benzofurans; D015415:Biomarkers; C073339:usnic acid