Application of ultra high performance liquid chromatography- mass spectrometry to metabolomics study of drug-induced hepatotoxicity
LIU Xiaoyan1, LIU Yanqiu2, CHENG Mengchun1, XIAO Hongbin1,3
1. Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China;
2. College (Institute) of Integrative Medicine, Dalian Medical University, Dalian 116044, China;
3. Beijing University of Chinese Medicine, Beijing 100029, China
Drug-induced hepatotoxicity is a worldwide health issue. And diagnosing the injury in the early stage is still a challenge in clinic. In this study, pattern recognition analysis of the ultra high performance liquid chromatography-mass spectrometry (UPLC-MS) of hepatocytes HL7702 was performed to develop differential metabolites related to hepatotoxicity induced by hepatotoxicants, including carbon tetrachloride (CCl4), acetaminophen (APAP), emodin, aristolochic acid (AA) and triptolide. Hepatocytes injuries were induced by 48 h of treatment with CCl4 (4 mmol/L), APAP (6.5 mmol/L), emodin (14 μmol/L), AA (35 μmol/L) and triptolide (18 nmol/L), separately. Global metabolomics profiling, multivariate analysis and database searching were performed to discover common differential metabolites for live injury. The positive hepatoprotective drug, bifendate, was used to repair triptolide induced hepatocytes injury, and bifendate-induced changes of hepatotoxicity-related metabolites were investigated. In the results, fatty acid oxidation and cellular oxidative stress-related metabolites, including nicotinamide adenine dinucleotide and glutathione were significantly changed between the control and hepatotoxicant-treated groups, and after treatment with bifendate, those perturbed metabolites all partly returned to normal level. In conclusion, we discovered potential hepatotoxicity-related metabolites that could be used to evaluate hepatotoxicity induced by chemicals, drugs and traditional Chinese medicines. This study also proved that metabolomics is one of the effective tools to investigate drug-induced hepatotoxicity.
LIU Xiaoyan,LIU Yanqiu,CHENG Mengchun et al. Application of ultra high performance liquid chromatography- mass spectrometry to metabolomics study of drug-induced hepatotoxicity[J]. Chinese Journal of Chromatography, 2015, 33(7): 683-690.