Citation: LIU Xiaoyan, LIU Yanqiu, CHENG Mengchun, XIAO Hongbin. 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. doi: 10.3724/SP.J.1123.2015.04007 shu

Application of ultra high performance liquid chromatography- mass spectrometry to metabolomics study of drug-induced hepatotoxicity

1.
1. Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China;

Corresponding author: XIAO Hongbin,
Received Date: 3 April 2015

Fund Project: 国家科技重大专项(2014ZX09304307-001-006). (2014ZX09304307-001-006)

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.
- ultra high performance liquid chromatography-mass spectrometry (UPLC-MS),
- metabolomics,
- hepatotoxicity
1. [1]
  [1] Beger R D, Sun J, Schnackenberg L K. Toxicol Appl Pharm, 2010, 243(2): 154
2. [2]
  [2] Fung M. Drug Inf J, 2001, 35(1): 293
3. [3]
  [3] Xu X, Qu C Q. Medical Recapitulate (徐鑫, 屈彩芹. 医学综述), 2008, 14(5): 747
4. [4]
  [4] Yu X W, Wu Q, Lü W, et al. Chinese Journal of Chromatography (余欣尉, 吴谦, 吕望, 等. 色谱), 2013, 31(7): 691
5. [5]
  [5] Li Y J, Zhang C L, Zhang H, et al. Chinese Journal of Chromatography (李艳杰, 张春兰, 张晗, 等. 色谱), 2014, 32(5): 464
6. [6]
  [6] Shi D D, Kuang Y Y, Wang G M, et al. Chinese Journal of Chromatography (史栋栋, 况媛媛, 王桂明, 等. 色谱), 2014, 32(3): 278
7. [7]
  [7] Peng S Y, Yan L J, Zhang J, et al. Chinese Journal of Chromatography (彭思远, 严丽娟, 张洁, 等. 色谱), 2012, 30(2): 123
8. [8]
  [8] Kim K B, Chung M W, Um S Y, et al. Metabolomics, 2008, 4(4): 377
9. [9]
  [9] Yang L, Xiong A, He Y, et al. Chem Res Toxicol, 2008, 21(12): 2280
10. [10]
  [10] Yamazaki M, Miyake M, Sato H, et al. Toxicol Appl Pharm, 2013, 268(1): 79
11. [11]
  [11] Li X, Zhang F, Wang D, et al. J Pharmaceut Biomed Anal, 2014, 89: 42
12. [12]
  [12] Kim J W, Ryu S H, Kim S, et al. Anal Chem, 2013, 85(23): 11326
13. [13]
  [13] Wang L, Yao D, Chen C. FASEB J, 2013, 27
14. [14]
  [14] Xiong Y H, Xu Y, Yang L, et al. J Appl Toxicol, 2014, 34(2): 149
15. [15]
  [15] Shaw D. Planta Medica, 2010, 76(17): 2012
16. [16]
  [16] Huang T C, Chen S M, Li Y C, et al. Biomed Chromatogr, 2013, 27(9): 1100
17. [17]
  [17] Dettmer K, Nuernberger N, Kaspar H, et al. Anal Bioanal Chem, 2011, 399(3): 1127
18. [18]
  [18] Tautenhahn R, Patti G J, Rinehart D, et al. Anal Chem, 2012, 84(11): 5035
19. [19]
  [19] Chen J, Zhao X, Fritsche J, et al. Anal Chem, 2008, 80(4): 1280
20. [20]
  [20] Shen G, Chen Y, Sun J, Zhang R, et al. J Proteome Res, 2011, 10(4): 1953
21. [21]
  [21] Chan E C Y, Pasikanti K K, Nicholson J K. Nat Protoc, 2011, 6(10): 1483
22. [22]
  [22] Peng S, Yan L, Zhang J, et al. J Pharmaceut Biomed Anal, 2013, 86: 56
23. [23]
  [23] Sakagami H, Sugimoto M, Tanaka S, et al. Metabolomics, 2014, 10(2): 270
24. [24]
  [24] Amet Y, Zerilli A, Goasduff T, et al. Biochem Pharmacol, 1997, 54(8): 947
25. [25]
  [25] Matsunaga I, Sumimoto T, Ueda A, et al. Lipids, 2000, 35(4): 365
26. [26]
  [26] Amet Y F, Adas A A. Alcohol Clin Exp Res, 1998, 22(7): 1493
27. [27]
  [27] Ana Carla B B, Fabricio B, Livia B, et al. Acta Pharmacol Sin, 2009, 30(1): 90
28. [28]
  [28] Liu T F, Vachharajani V T, Yoza B K, et al. J Biol Chem, 2012, 287(31): 25758
29. [29]
  [29] Diaz Ochoa J G, Bucher J, Pery A R R, et al. Front Pharmacol, 2012, 3: 204
30. [30]
  [30] Pan S Y, Yang R, Dong H, et al. Eur J Pharmacol, 2006, 552(1/3): 170
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