Idiosyncratic Drug-Induced Liver Injury and the Role of Inflammatory Stress with an Emphasis on an Animal Model of Trovafloxacin Hepatotoxicity
Open accessAbstract
Idiosyncratic adverse drug reactions (IADRs) occur in a minority of patients yet account for the majority of postmarketing use restrictions by the Food and Drug Administration. Despite the impact of these toxicities, the underlying mechanisms are still poorly understood. Animal models of IADRs would be beneficial in understanding mechanisms and in developing assays with predictive potential. Recent work exploring the interactions between inflammatory stress and drugs associated with human idiosyncratic drug-induced liver injury (IDILI) has led to the development of the first animal models that apply to a range of drugs. Here, we discuss hypotheses for the mechanisms of IDILI and focus on a murine model of trovafloxacin-induced hepatotoxicity as an example related to the inflammatory stress hypothesis.
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Trovafloxacin is believed to have an inflammatory component to its toxicity, potentially mediated by Kupffer cells, but this is only seen in animal models if an inflammatory stimulant such as LPS is co-administered.
“the third-generation anti-infective trovafloxacin is believed to have an inflammatory component to its toxicity, potentially mediated by Kupffer cells, but this is only seen in animal models if an inflammatory stimulant such as lipopolysaccharide (LPS) is co-administered39.”
From Performance assessment and economic analysis of a human Liver-Chip for predictive toxicology (2022) · cites this paper as [39]
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- Authors
- Shaw, P. J., Ganey, P. E., & Roth, R. A.
- Affiliations
- St. Jude Children's Research Hospital (US)
- Michigan State University (US)
- Venue
- Toxicological Sciences
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-06-10
- Volume
- 118
- Issue
- 1
- Pages
- 7-18
- ISSN
- 1096-0929 (ISSN-L)
- 1096-6080
- PMC
- PMC2955207
- OpenAlex
- W2126028929
- Cited by
- 123
- References
- 6
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 5 · 2022: 7 · 2021: 12 · 2020: 13 · 2019: 7 · 2018: 3 · 2017: 12 · 2016: 15 · 2015: 12 · 2014: 3 · 2013: 9 · 2012: 10
- FWCI
- 1.34
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Toxicological Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK061315)
- National Institute of Environmental Health Sciences (R01ES004139)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Pharmacology › Drug-Induced Adverse Reactions
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Keywords
- idiosyncratic drug-induced liver injury, idiosyncratic drug reactions, mouse model
- MeSH terms
- Animals, Anti-Infective Agents, Disease Models, Animal, Humans, Inflammation, Naphthyridines, Stress, Physiological, Fluoroquinolones, Chemical and Drug Induced Liver Injury, Drug-Related Side Effects and Adverse Reactions
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