Cited by 403Drug-Induced Hepatotoxicity and ProtectionPharmacogenetics and Drug MetabolismPharmacovigilance and Adverse Drug Reactions

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Diclofenac-induced liver injury: a paradigm of idiosyncratic drug toxicity

Boelsterli, U·2003·Toxicology and Applied Pharmacology

DOI 10.1016/s0041-008x(03)00368-5

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Abstract

The nonsteroidal antiinflammatory drug diclofenac causes rare but significant cases of serious hepatotoxicity, typically with a delayed onset (>1-3 months). Because there is no simple dose relationship and because liver injury cannot be reproduced in current animal models, individual patient-specific susceptibility factors have been evoked to account for the increased risk. While these patient factors have remained undefined, a number of molecular hazards have been characterized. Among these are metabolic factors (bioactivation by hCYP2C9 or hCYP3A4 to thiol-reactive quinone imines, activation by hUGT2B7 to protein-reactive acyl glucuronides and iso-glucuronides, and 4'-hydroxylation secondary to diclofenac glucuronidation), as well as kinetic factors (Mrp2-mediated concentrative transport of diclofenac metabolites into bile). From the toxicodynamic view, both oxidative stress (caused by putative diclofenac cation radicals or nitroxide and quinone imine-related redox cycling) and mitochondrial injury (protonophoretic activity and opening of the permeability transition pore) alone or in combination have been implicated in diclofenac toxicity. In some cases, immune-mediated liver injury is involved, inferred from inadvertent rechallenge data and from a number of experiments demonstrating T cell sensitization. Why certain underlying diseases (e.g., osteoarthritis) also increase the susceptibility to diclofenac hepatotoxicity is not clear. To date, cumulative damage to mitochondrial targets seems a plausible putative mechanism to explain the delayed onset of liver failure, perhaps even superimposed on an underlying silent mitochondrial abnormality. Increased efforts to identify both patient-specific risk factors and disease-related factors will help to define patient subsets at risk as well as increase the predictability of unexpected hepatotoxicity in drug development.

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ACETAMINOPHEN-INDUCED HEPATOTOXICITY
James, L. P., Mayeux, P. R., & Hinson, J. (2003) · Drug Metabolism and Disposition · doi:10.1124/dmd.31.12.1499 · Cited by 1,033
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Sgro, C., Clinard, F., Ouazir, K., Chanay, H., Allard, C., Guilleminet, C., Lenoir, C., Lemoine, A., & Hillon, P. (2002) · Hepatology · doi:10.1053/jhep.2002.34857 · Cited by 716
Hepatotoxicity. The adverse effects of drugs and other chemicals on the liver
(1980) · Food and Cosmetics Toxicology · doi:10.1016/0015-6264(80)90206-0 · Cited by 691
Modulation of the Mitochondrial Permeability Transition Pore by Pyridine Nucleotides and Dithiol Oxidation at Two Separate Sites
Costantini, P., Chernyak, B. V., Petronilli, V., & Bernardi, P. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.12.6746 · Cited by 516
Acyl Glucuronides Revisited: Is the Glucuronidation Proces a Toxification as Well as a Detoxification Mechanism?
Spahn-Langguth, H., & Benet, L. Z. (1992) · Drug Metabolism Reviews · doi:10.3109/03602539208996289 · Cited by 407
Clustering of Hepatotoxins Based on Mechanism of Toxicity Using Gene Expression Profiles
Waring, J. F., Jolly, R. A., Ciurlionis, R., Lum, P. Y., Præstgaard, J., Morfitt, D. C., Buratto, B., Roberts, C., Schadt, E. E., & Ulrich, R. G. (2001) · Toxicology and Applied Pharmacology · doi:10.1006/taap.2001.9243 · Cited by 376
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Faed, E. M. (1984) · Drug Metabolism Reviews · doi:10.3109/03602538409033562 · Cited by 299
Diclofenac-associated hepatotoxicity: Analysis of 180 cases reported to the food and drug administration as adverse reactions
Banks, A. T., Zimmerman, H. J., Ishak, K. G., & Harter, J. G. (1995) · Hepatology · doi:10.1002/hep.1840220320 · Cited by 296
Drug-Induced Liver Disorders
Kaplowitz, N. (2001) · Drug Safety · doi:10.2165/00002018-200124070-00001 · Cited by 261

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Authors: Boelsterli, U.
Affiliations: University of Basel (CH)
Corresponding author: Boelsterli, U
Venue: Toxicology and Applied Pharmacology
Publisher: Elsevier BV
Published: 2003-11-01
Volume: 192
Issue: 3
Pages: 307-322
ISSN: 0041-008X (ISSN-L)
DOI: 10.1016/s0041-008x(03)00368-5
OpenAlex: W2003181581
Cited by: 403
References: 101
Citations by year: 2026: 11 · 2025: 10 · 2024: 8 · 2023: 17 · 2022: 12 · 2021: 20 · 2020: 17 · 2019: 18 · 2018: 15 · 2017: 23 · 2016: 30 · 2015: 17 · 2014: 17 · 2013: 20 · 2012: 20
FWCI: 8.24
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Toxicology and Applied Pharmacology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
Keywords: diclofenac, hepatotoxicity, idiosyncratic drug toxicity, nonsteroidal anti-inflammatory drugs, CYP2C9, CYP3A4, UGT2B7, quinone imines, acyl glucuronides, MRP2, bile transport, oxidative stress, mitochondrial injury, mitochondrial permeability transition pore, immune-mediated liver injury, T cell sensitization, osteoarthritis, toxicodynamics
MeSH terms: Animals, Anti-Inflammatory Agents, Non-Steroidal, Diclofenac, Humans, Chemical and Drug Induced Liver Injury, Drug-Related Side Effects and Adverse Reactions

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Diclofenac-induced liver injury: a paradigm of idiosyncratic drug toxicity

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