Metabolomic approaches in the discovery of potential urinary biomarkers of drug-induced liver injury (DILI)

Abstract

Drug-induced liver injury (DILI) is a major safety issue during drug development, as well as the most common cause for the withdrawal of drugs from the pharmaceutical market. The identification of DILI biomarkers is a labor-intensive area. Conventional biomarkers are not specific and often only appear at significant levels when liver damage is substantial. Therefore, new biomarkers for early identification of hepatotoxicity during the drug discovery process are needed, thus resulting in lower development costs and safer drugs. In this sense, metabolomics has been increasingly playing an important role in the discovery of biomarkers of liver damage, although the characterization of the mechanisms of toxicity induced by xenobiotics remains a huge challenge. These new-generation biomarkers will offer obvious benefits for the pharmaceutical industry, regulatory agencies, as well as a personalized clinical follow-up of patients, upon validation and translation into clinical practice or approval for routine use. This review describes the current status of the metabolomics applied to the early diagnosis and prognosis of DILI and in the discovery of new potential urinary biomarkers of liver injury.

Keywords:

• Drug-induced liver injury
• hepatotoxicity
• metabolomics
• urinary biomarkers
• conventional biomarkers

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Acknowledgements

This work received financial support from the European Union (FEDER funds POCI/01/0145/FEDER/07728) and National funds (FCT/MEC, Fundação para a Ciência e a Tecnologia and Ministério da Educação e Ciência) under the Partnership Agreement PT2020 UID/MULTI/04378/2013. We also thank the ‘Comissão de Coordenação e Desenvolvimento Regional do Norte (CCDRN)/NORTE2020/Portugal 2020’ through the project: DESignBIOtecHealth ? New Technologies for three Health Challenges of Modern Societies: Diabetes, Drug Abuse and Kidney Diseases) for its financial support. A.M.A. also thanks Fundação para a Ciência e Tecnologia for her PhD grant (SFRH/BD/107708/2015).

The authors also gratefully acknowledge the very helpful suggestions made by the reviewers anonymously selected by the Editor. The comments helped improve the quality of the revised paper.

Declaration of interest

All authors have read the journal’s policy on disclosure of potential conflicts of interest and have none to declare. Furthermore, none of the authors has appeared in the last five years in legal or regulatory proceedings that involved the contents of this paper.

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