The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Cellular Imaging Predictions of Clinical Drug-Induced Liver Injury
Open accessAbstract
Drug-induced liver injury (DILI) is the most common adverse event causing drug nonapprovals and drug withdrawals. Using drugs as test agents and measuring a panel of cellular phenotypes that are directly linked to key mechanisms of hepatotoxicity, we have developed an in vitro testing strategy that is predictive of many clinical outcomes of DILI. Mitochondrial damage, oxidative stress, and intracellular glutathione, all measured by high content cellular imaging in primary human hepatocyte cultures, are the three most important features contributing to the hepatotoxicity prediction. When applied to over 300 drugs and chemicals including many that caused rare and idiosyncratic liver toxicity in humans, our testing strategy has a true-positive rate of 50-60% and an exceptionally low false-positive rate of 0-5%. These in vitro predictions can augment the performance of the combined traditional preclinical animal tests by identifying idiosyncratic human hepatotoxicants such as nimesulide, telithromycin, nefazodone, troglitazone, tetracycline, sulindac, zileuton, labetalol, diclofenac, chlorzoxazone, dantrolene, and many others. Our findings provide insight to key DILI mechanisms, and suggest a new approach in hepatotoxicity testing of pharmaceuticals.
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Cites
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Concordance of the toxicity of pharmaceuticals in humans and in animals
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Idiosyncratic drug hepatotoxicity
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Hewitt, N. J., Gómez Lechón, M. J., Houston, J. B., Hallifax, D., Brown, H. S., Maurel, P., Kenna, J. G., Gustavsson, L., Lohmann, C., Skonberg, C., et al. (2007) · Drug Metabolism Reviews · doi:10.1080/03602530601093489 · Cited by 735
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Why Drugs Fail - A Study on Side Effects in New Chemical Entities
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“It is the leading cause in acute liver failures that necessitate organ transplants, safety recalls from the world-wide pharmaceutical market, nonapprovable decisions regarding new drug applications (NDAs), and internal drug development failures among all major pharmaceutical companies (Giacomini et al., 2007; Holt and…”
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Cited by
Godoy, P., Hewitt, N. J., Albrecht, U., Andersen, M. E., Ansari, N., Bhattacharya, S., Bode, J. G., Bolleyn, J., Borner, C., Böttger, J., et al. (2013) · Archives of Toxicology · doi:10.1007/s00204-013-1078-5 · Cited by 1,280
Self-citationAdvances in organ-on-a-chip engineering
Zhang, B., Korolj, A., Lai, B. F. L., & Radisic, M. (2018) · Nature Reviews Materials · doi:10.1038/s41578-018-0034-7 · Cited by 1,017
Gerets, H. H. J., Tilmant, K., Gerin, B., Chanteux, H., Depelchin, B. O., Dhalluin, S., & Atienzar, F. A. (2012) · Cell Biology and Toxicology · doi:10.1007/s10565-011-9208-4 · Cited by 698
Organ-on-a-chip devices advance to market
Zhang, B., & Radisic, M. (2017) · Lab on a Chip · doi:10.1039/c6lc01554a · Cited by 437
FDA-approved drug labeling for the study of drug-induced liver injury
Chen, M., Vijay, V., Shi, Q., Liu, Z., Fang, H., & Tong, W. (2011) · Drug Discovery Today · doi:10.1016/j.drudis.2011.05.007 · Cited by 406
Metadata
- Authors
- Xu, J. J., Henstock, P. V., Dunn, M. C., Smith, A. R., Chabot, J. R., & de Graaf, D.
- Venue
- Toxicological Sciences
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-06-03
- Volume
- 105
- Issue
- 1
- Pages
- 97-105
- ISSN
- 1096-0929 (ISSN-L)
- 1096-6080
- OpenAlex
- W2132272495
- Cited by
- 492
- References
- 8
- FWCI
- 18.48
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Xu, J. J., Henstock, P. V., Dunn, M. C., Smith, A. R., Chabot, J. R., & de Graaf, D. (2008). Cellular Imaging Predictions of Clinical Drug-Induced Liver Injury. Toxicological Sciences. https://doi.org/10.1093/toxsci/kfn109
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
