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LC–MS-Based Metabolomics in the Study of Drug-Induced Liver Injury

  • Pharmacometabolomics and Toxicometabolomics (Chi Chen, Section Editor)
  • Published:
Current Pharmacology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Metabolomics is the systematic and comparative study of the levels of small-molecule metabolites in samples under various conditions. In biological system, metabolites play a critical role in a diversity of cellular functions. Metabolomics has been widely employed in toxicology and other fields. The purpose of this review is to summarize recent literatures on the application of LC–MS-based metabolomics in drug bioactivation and drug-induced liver injury (DILI) and to discuss their challenges in the field of toxicology.

Recent Findings

The emerging metabolomics could provide us a comprehensive view of novel biochemical sequelae in the cells, tissues, and organisms following toxicant administration. This article reviews LC–MS-based metabolomics in identification of biomarkers of drug toxicity and elucidating mechanisms of toxicity reported in recent years. This review also discusses the application of metabolomics combined with genomics or proteomics in the research field of DILI.

Summary

LC–MS-based metabolomics has a great potential in drug metabolism, identification of biomarkers of cause and/or effect, and revealing the novel mechanisms of drug toxicity. In the future, metabolomics integrating with other omics can serve as an effective tool for investigating the mechanisms of drug toxicity.

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Abbreviations

AcHZ:

Acetylhydrazine

AGM:

Agomelatine

ALAS:

Aminolevulinic acid synthase

ALA:

Aminolevulinic acid

ALT:

Alanine aminotransferase

APAP:

Acetaminophen

Cd:

Cadmium

CYP450:

Cytochromes P450

DILI:

Drug-induced liver injury

ESI:

Electrospray ionization

GSH:

Glutathione

HLM:

Human liver microsomes

hPXR:

Pregnane X receptor humanized

INH:

Isoniazid

MDA:

Multivariate data analysis

MDF:

Mass defect filtering

MRM:

Multiple reaction monitoring

NADPH:

Reduced nicotinamide adenine dinucleotide phosphate

OPLS-DA:

Orthogonal projection to latent structures-discriminant analysis

PMCol:

Pentamethyl-6-chromanol

PPIX:

Protoporphyrin IX

QTOFMS:

Quadrupole time of flight mass spectrometry

RIF:

Rifampicin

UPLC:

Ultra-performance liquid chromatography

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Acknowledgements

We would like to thank Dr. Xiaochao Ma at University of Pittsburgh for his kind suggestion and support for this research.

Funding

This work was supported by the Cancer Prevention & Research Institute of Texas (RP160805), Welch Foundation Grant (H-Q-0042) to Dr. Martin M. Matzuk, and NIH R01 (AR063686) to Zhaoyong Hu.

Author information

Authors and Affiliations

  1. Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, 563000, Guizhou, China

    Yuanfu Lu

  2. College of Pharmacy, Taishan Medical University, Tai’an, 271016, Shandong, China

    Xue-Mei Zhao

  3. Nephrology Division, Department of Medicine, Baylor College of Medicine, Houston, TX, 77030, USA

    Zhaoyong Hu

  4. Department of Physiology and Neurobiology, and The Institute for Systems Genomics, University of Connecticut, Storrs, CT, USA

    Li Wang

  5. Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA

    Li Wang

  6. Department of Internal Medicine, Section of Digestive Diseases, Yale University, New Haven, CT, USA

    Li Wang

  7. Center for Drug Discovery, Baylor College of Medicine, Houston, TX, 77030, USA

    Feng Li

  8. Department of Molecular and Cellular Biology, Advance Technology Core, Baylor College of Medicine, Houston, TX, 77030, USA

    Feng Li

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  1. Yuanfu Lu
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Correspondence to Feng Li.

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Lu, Y., Zhao, XM., Hu, Z. et al. LC–MS-Based Metabolomics in the Study of Drug-Induced Liver Injury. Curr Pharmacol Rep 5, 56–67 (2019). https://doi.org/10.1007/s40495-018-0144-3

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