ArticleThe Journal of biological chemistry2015
Nonantibiotic Effects of Fluoroquinolones in Mammalian Cells.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
44 citing papers in PubMed, 4 syntheses or guidelines pooled it, 107 citations in OpenAlex.
- Effects of Fluoroquinolones on Aortic Aneurysm or Dissection Processes: A Systematic Review and Meta-Analysis.Reviews in cardiovascular medicine · 2026Pooled it
- The association between fluoroquinolones and aortic dissection and aortic aneurysms: a systematic review and meta-analysis.Scientific reports · 2021Pooled it
- Fluoroquinolones and the Risk of Aortic Aneurysm or Aortic Dissection: A Systematic Review and Meta-Analysis.Cardiovascular & hematological agents in medicinal chemistry · 2019Pooled it
- Fluoroquinolone-Associated Tendinopathy of the Hand and Wrist: A Systematic Review and Case Report.Hand (New York, N.Y.) · 2017Pooled it
- Safety and Efficacy of PrimeC in Amyotrophic Lateral Sclerosis: The PARADIGM Randomized Clinical Trial.JAMA neurology · 2026Trial
- Effects of fluoroquinolone antibiotics on extracellular matrix-related phenotypes in tendon cells.Scientific reports · 2026Article
- Review
- Fluoroquinolone-Induced Achilles Tendon Damage: Structural and Biochemical Insights into Collagen Type I Alterations.International journal of molecular sciences · 2025Review
- Fluoroquinolone-Associated Disability: A Rodent Model Reveals Transient Neuropsychiatric and Persistent Gastrointestinal Effects of Low-Dose Ciprofloxacin.Pharmaceuticals (Basel, Switzerland) · 2025Article
- High-sensitivity detection of norfloxacin in milk and water: a bismuth-based photoelectrochemical aptasensing platform.Mikrochimica acta · 2025Article
- Chemical Proteomics Reveals Human Off-Targets of Fluoroquinolone Induced Mitochondrial Toxicity.Angewandte Chemie (International ed. in English) · 2025Article
- Elucidating the Synergistic Effect of the PrimeC Combination for Amyotrophic Lateral Sclerosis in Human Induced Pluripotent Stem Cell-Derived Motor Neurons and Mouse Models.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Effect of FluoRoquinolones on Aortic Growth, aortic stIffness and wave refLEctionS (FRAGILES study).Life (Basel, Switzerland) · 2024Article
- A Review on Fluoroquinolones' Toxicity to Freshwater Organisms and a Risk Assessment.Journal of xenobiotics · 2024Review
- Isolation, characterization and functional analysis of a bacteriophage targeting Culex pipiens pallens resistance-associated Aeromonas hydrophila.Parasites & vectors · 2024Article
- Deferasirox and Ciprofloxacin: Potential Ternary Complex Formation With Ferric Iron, Pharmacodynamic, and Pharmacokinetic Interactions.TheScientificWorldJournal · 2024Article
- An In Vivo Whole-Transcriptomic Approach to Assess Developmental and Reproductive Impairments Caused by Flumequine inInternational journal of molecular sciences · 2023Article
- A ciprofloxacin derivative with four mechanisms of action overcomes paclitaxel resistance in p53-mutant and MDR1 gene-expressing type II human endometrial cancer.Biomaterials · 2023Article
- Article
- Overview of Side-Effects of Antibacterial Fluoroquinolones: New Drugs versus Old Drugs, a Step Forward in the Safety Profile?Pharmaceutics · 2023Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Fluoroquinolones (FQ) are powerful broad-spectrum antibiotics whose side effects include renal damage and, strangely, tendinopathies. The pathological mechanisms underlying these toxicities are poorly understood. Here, we show that the FQ drugs norfloxacin, ciprofloxacin, and enrofloxacin are powerful iron chelators comparable with deferoxamine, a clinically useful iron-chelating agent. We show that iron chelation by FQ leads to epigenetic effects through inhibition of α-ketoglutarate-dependent dioxygenases that require iron as a co-factor. Three dioxygenases were examined in HEK293 cells treated with FQ. At sub-millimolar concentrations, these antibiotics inhibited jumonji domain histone demethylases, TET DNA demethylases, and collagen prolyl 4-hydroxylases, leading to accumulation of methylated histones and DNA and inhibition of proline hydroxylation in collagen, respectively. These effects may explain FQ-induced nephrotoxicity and tendinopathy. By the same reasoning, dioxygenase inhibition by FQ was predicted to stabilize transcription factor HIF-1α by inhibition of the oxygen-dependent hypoxia-inducible transcription factor prolyl hydroxylation. In dramatic contrast to this prediction, HIF-1α protein was eliminated by FQ treatment. We explored possible mechanisms for this unexpected effect and show that FQ inhibit HIF-1α mRNA translation. Thus, FQ antibiotics induce global epigenetic changes, inhibit collagen maturation, and block HIF-1α accumulation. We suggest that these mechanisms explain the classic renal toxicities and peculiar tendinopathies associated with FQ antibiotics.
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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.