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Biomedical Research International


Idiosyncratic drug-induced liver injury (IDILI) is a significant source of drug recall and acute liver failure (ALF) in the United States. While current drug development processes emphasize general toxicity and drug metabolizing enzyme- (DME-) mediated toxicity, it has been challenging to develop comprehensive models for assessing complete idiosyncratic potential. In this review, we describe the enzymes and proteins that contain polymorphisms believed to contribute to IDILI, including ones that affect phase I and phase II metabolism, antioxidant enzymes, drug transporters, inflammation, and human leukocyte antigen (HLA). We then describe the various assays that have been developed to detect individual reactions focusing on each of the mechanisms described in the background. Finally, we examine current trends in developing comprehensive models for examining these mechanisms. There is an urgent need to develop a panel of multiparametric assays for diagnosing individual toxicity potential.


The authors are grateful for the funding from the National Institutes of Health (NIEHS R01ES025779) and institutional funds from Cleveland State University (Faculty Research Development and Faculty Innovation Fund).

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Alexander D. Roth and Moo-Yeal Lee, “Idiosyncratic Drug-Induced Liver Injury (IDILI): Potential Mechanisms and Predictive Assays,” BioMed Research International, vol. 2017, Article ID 9176937, 23 pages, 2017.

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Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.