Metabolomics Investigations of Drug-induced Hepatotoxicity
Drug-induced liver injury (DILI) is a leading cause of drug development failure and withdrawal from market, and it accounts for as much as 50% of clinical liver failures. Its underlying biochemical mechanisms can be possibly many, but there is a lack of biomarkers for prediction and prevention. This chapter will review likely biochemical mechanisms commonly encountered in DILI cases with illustration using well-known examples of drugs of DILI problems. Metabolomics is introduced later with examples to demonstrate its promising potential for dissecting DILI biochemical mechanisms and looking for small-molecule biomarkers. Small-molecule metabolites are not only closely related to toxicity biochemistry but also readily translatable across different animal species and humans.