ArticleToxicological sciences : an official journal of the Society of Toxicology2009
Trovafloxacin enhances TNF-induced inflammatory stress and cell death signaling and reduces TNF clearance in a murine model of idiosyncratic hepatotoxicity.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 52 citations in OpenAlex.
- Evaluation of drug-induced liver toxicity of trovafloxacin and levofloxacin in a human microphysiological liver model.Scientific reports · 2023Article
- Performance assessment and economic analysis of a human Liver-Chip for predictive toxicology.Communications medicine · 2022Article
- Icariside I specifically facilitates ATP or nigericin-induced NLRP3 inflammasome activation and causes idiosyncratic hepatotoxicity.Cell communication and signaling : CCS · 2021Article
- What have we learned from animal models of idiosyncratic, drug-induced liver injury?Expert opinion on drug metabolism & toxicology · 2020Review
- Managing the challenge of drug-induced liver injury: a roadmap for the development and deployment of preclinical predictive models.Nature reviews. Drug discovery · 2020Review
- Dynamic imaging of adaptive stress response pathway activation for prediction of drug induced liver injury.Archives of toxicology · 2018Article
- From the Cover: Three-Dimensional (3D) HepaRG Spheroid Model With Physiologically Relevant Xenobiotic Metabolism Competence and Hepatocyte Functionality for Liver Toxicity Screening.Toxicological sciences : an official journal of the Society of Toxicology · 2017Article
- Article
- Trovafloxacin enhances lipopolysaccharide-stimulated production of tumor necrosis factor-α by macrophages: role of the DNA damage response.The Journal of pharmacology and experimental therapeutics · 2014Article
- Trovafloxacin potentiation of lipopolysaccharide-induced tumor necrosis factor release from RAW 264.7 cells requires extracellular signal-regulated kinase and c-Jun N-Terminal Kinase.The Journal of pharmacology and experimental therapeutics · 2014Article
- Molecular mechanisms of hepatocellular apoptosis induced by trovafloxacin-tumor necrosis factor-alpha interaction.Toxicological sciences : an official journal of the Society of Toxicology · 2014Article
- Tumor necrosis factor-alpha potentiates the cytotoxicity of amiodarone in Hepa1c1c7 cells: roles of caspase activation and oxidative stress.Toxicological sciences : an official journal of the Society of Toxicology · 2013Article
- Current challenges and controversies in drug-induced liver injury.Drug safety · 2012Article
- Hepatic safety of antibiotics used in primary care.The Journal of antimicrobial chemotherapy · 2011Review
- Comparison of TNFα to lipopolysaccharide as an inflammagen to characterize the idiosyncratic hepatotoxicity potential of drugs: Trovafloxacin as an example.International journal of molecular sciences · 2010Article
- Idiosyncratic drug-induced liver injury and the role of inflammatory stress with an emphasis on an animal model of trovafloxacin hepatotoxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2010Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Therapy employing the fluoroquinolone antibiotic, trovafloxacin (TVX) was curtailed due to idiosyncratic hepatotoxicity. Previous studies in mice showed that a nonhepatotoxic inflammatory stress induced by tumor necrosis factor alpha (TNF) synergized with a nonhepatotoxic dose of TVX to cause liver injury. The purpose of this study was to explore mechanisms by which TVX interacts with TNF to cause liver injury. TVX pretreatment prolonged the peak of plasma TNF after its administration. This prolongation of TNF by TVX was critical to the development of hepatotoxicity. The prolongation of TNF concentration in plasma was primarily due to reduced clearance when compared with secondary biosynthesis. TNF is cleared from plasma by binding to soluble TNF receptors (TNFRs) which are eliminated by the kidney; however, the plasma concentrations of soluble TNFRs were not reduced, and biomarkers of renal dysfunction were not elevated in TVX/TNF-treated mice. Two injections of TNF mimicked the prolongation of the TNF peak by TVX and caused liver injury, but injury was less severe than after TVX/TNF coexposure. TVX enhanced the induction of proinflammatory cytokines by TNF. Additionally, TVX sensitized Hepa1c1c7 cells to TNF-induced killing in a concentration-dependent manner and increased both potency and efficacy of TNF to activate effector caspases that were critically involved in cell death from TVX/TNF coexposure. In summary, TVX reduced the clearance of TNF independent of either receptor shedding or kidney dysfunction. Additionally, TVX interacted with TNF to enhance inflammation and sensitize hepatocytes to TNF-induced cell death.
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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.