ReviewDrug safety2002
Mechanisms of NSAID-induced hepatotoxicity: focus on nimesulide.
Review in Drug safety, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 154 citations in OpenAlex.
- A clinical and mechanistic study of topical borneol-induced analgesia.EMBO molecular medicine · 2017Trial
- Article
- Synthesis, characterization, biological evaluation, and molecular modeling of novel nimesulide urea derivatives as potential MetAP2 inhibitors.Scientific reports · 2026Article
- Hierarchical Mechanistic Modeling of Complex Toxicity Endpoints from Public Concentration-Response Data.Environmental science & technology · 2026Article
- Self-Medication with NSAIDs in Gondar city: prevalence, predictors, and public health implications.Scientific reports · 2025Article
- Safety Assessment of an Oral Therapeutic Dose of Firocoxib on Healthy Horses.Veterinary sciences · 2023Article
- MgIG exerts therapeutic effects on crizotinib-induced hepatotoxicity by limiting ROS-mediated autophagy and pyroptosis.Journal of cellular and molecular medicine · 2022Article
- Self-medication practice with analgesics (NSAIDs and acetaminophen), and antibiotics among nursing undergraduates in University College Farasan Campus, Jazan University, KSA.Annales pharmaceutiques francaises · 2021Article
- Serious liver injury induced by Nimesulide: an international collaborative study.Archives of toxicology · 2021Article
- Oxidative Stress in Drug-Induced Liver Injury (DILI): From Mechanisms to Biomarkers for Use in Clinical Practice.Antioxidants (Basel, Switzerland) · 2021Review
- Can Nimesulide Nanoparticles Be a Therapeutic Strategy for the Inhibition of the KRAS/PTEN Signaling Pathway in Pancreatic Cancer?Frontiers in oncology · 2021Review
- Diclofenac-induced cytotoxicity in cultured carp leukocytes.Physiological research · 2020Article
- Indomethacin Increases the Efficacy of Oxygen Utilization of Colonic Mitochondria and Uncouples Hepatic Mitochondria in Tissue Homogenates From Healthy Rats.Frontiers in medicine · 2020Article
- Impact of the World Health Organization Pain Treatment Guidelines and the European Medicines Agency Safety Recommendations on Nonsteroidal Anti-Inflammatory Drug Use in Lithuania: An Observational Study.Medicina (Kaunas, Lithuania) · 2018Observational
- Calcium Contributes to the Cytotoxic Interaction Between Diclofenac and Cytokines.Toxicological sciences : an official journal of the Society of Toxicology · 2016Article
- Nimesulide induced leukocytoclastic vasculitis and hepatitis: a case report.SpringerPlus · 2015Article
- Managing the challenge of chemically reactive metabolites in drug development.Nature reviews. Drug discovery · 2011Review
- Non-steroidal anti-inflammatory drugs: What is the actual risk of liver damage?World journal of gastroenterology · 2010Review
- Oxidative stress is important in the pathogenesis of liver injury induced by sulindac and lipopolysaccharide cotreatment.Toxicology · 2010Article
- Hepatotoxic interaction of sulindac with lipopolysaccharide: role of the hemostatic system.Toxicological sciences : an official journal of the Society of Toxicology · 2009Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with idiosyncratic hepatotoxicity in susceptible patients. The molecular mechanisms underlying this toxicity have not yet been fully elucidated. However, experimental evidence suggests that they include increased concentration of the drugs in the hepatobiliary compartment, formation of reactive metabolites that covalently modify proteins and produce oxidative stress, and mitochondrial injury. Genetic and/or acquired patient factors can either augment the pathways leading to hepatic toxicity or impede the protective and detoxifying pathways. An example is nimesulide, a selective cyclo-oxygenase-2 inhibitor widely used for the treatment of inflammatory and pain conditions, which has been recently associated with rare but serious and unpredictable adverse reactions in the liver (increases in serum aminotransferase activities, hepatocellular necrosis, and/or intrahepatic cholestasis). Similar to other drugs causing idiosyncratic hepatotoxicity, both the molecule and the patient contribute to the hazard. Here, the weakly acidic sulfonanilide drug undergoes bioreductive metabolism of the nitroarene group to reactive intermediates that have been implicated in oxidative stress, covalent binding, and mitochondrial injury. It is only in a small number of susceptible patients, however, that genetic or nongenetic factors will cause this potential toxicity to become clinically manifest. In view of the very large recipient population, the incidence of nimesulide-induced liver injury has been low (approximately 0.1 per 100,000 patients treated). Although this estimation is based on spontaneous reporting data versus sales units and needs correction due to the classical bias of this system, the type and incidence of these rare but severe hepatic adverse reactions are comparable to that of other NSAIDs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.