ArticleArchives of toxicology2018
Polymyxin B causes DNA damage in HK-2 cells and mice.
Article in Archives of toxicology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 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
20 citing papers in PubMed, 28 citations in OpenAlex.
- Systems-Level Phosphoproteomic and RPPA Profiling Reveals Stress and DNA Damage Signalling as Early Drivers of Polymyxin B Neurotoxicity.Molecular neurobiology · 2026Article
- Synergistic antimicrobial potential of Cinnamomum triplinerve essential oils combined with polymyxin B against multidrug-resistant Klebsiella pneumoniae.Scientific reports · 2026Article
- Lipopeptide Engineering: From Natural Origins to Rational Design Against Antimicrobial Resistance.Antibiotics (Basel, Switzerland) · 2026Review
- Molecular mechanisms attributed to colistin renal proximal tubular epithelial cytotoxicity.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2025Review
- A Synthetic Phage-Peptide Conjugate as a Potent Antibacterial Agent forACS central science · 2025Article
- Antimicrobial Peptide-Peptoid Macrocycles from the Polymyxin B2 Chemical Space.Angewandte Chemie (International ed. in English) · 2025Article
- Polymyxin B Peptide Hydrogel Coating: A Novel Approach to Prevent Ventilator-Associated Pneumonia.International journal of molecular sciences · 2024Article
- Recent Advances in the Development of Polymyxin Antibiotics: 2010-2023.ACS infectious diseases · 2024Review
- Synchrotron-based X-ray fluorescence microscopy reveals accumulation of polymyxins in single human alveolar epithelial cells.Antimicrobial agents and chemotherapy · 2023Article
- Transcriptomic Responses to Polymyxin B and Analogues in Human Kidney Tubular Cells.Antibiotics (Basel, Switzerland) · 2023Article
- Therapeutic Potential of an Azithromycin-Colistin Combination against XDRAntibiotics (Basel, Switzerland) · 2023Article
- Inwardly rectifying potassium channels mediate polymyxin-induced nephrotoxicity.Cellular and molecular life sciences : CMLS · 2022Article
- Polymyxin Induces Significant Transcriptomic Perturbations of Cellular Signalling Networks in Human Lung Epithelial Cells.Antibiotics (Basel, Switzerland) · 2022Article
- The polypeptide antibiotic polymyxin B acts as a pro-inflammatory irritant by preferentially targeting macrophages.The Journal of antibiotics · 2022Article
- Rescuing the Last-Line Polymyxins: Achievements and Challenges.Pharmacological reviews · 2021Review
- Heat Shock Proteins as Targets for Novel Antimalarial Drug Discovery.Advances in experimental medicine and biology · 2021Article
- Birch Pollen Induces Toll-Like Receptor 4-Dependent Dendritic Cell Activation Favoring T Cell Responses.Frontiers in allergy · 2021Article
- Effect of Different Dosage Frequency of Polymyxin B on Rat Nephrotoxicity.Drug design, development and therapy · 2021Article
- Polymyxins-Curcumin Combination Antimicrobial Therapy: Safety Implications and Efficacy for Infection Treatment.Antioxidants (Basel, Switzerland) · 2020Review
- Polymyxin Acute Kidney Injury: Dosing and Other Strategies to Reduce Toxicity.Antibiotics (Basel, Switzerland) · 2019Review
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Increasing incidence of multidrug-resistant bacteria presents an imminent risk to global health. Polymyxins are 'last-resort' antibiotics against Gram-negative 'superbugs'; however, nephrotoxicity remains a key impediment in their clinical use. Molecular mechanisms underlying this nephrotoxicity remain poorly defined. Here, we examined the pathways which led to polymyxin B induced cell death in vitro and in vivo. Human proximal tubular cells were treated with polymyxin B (12.5-100 μM) for up to 24 h and showed a significant increase in micronuclei frequency, as well as abnormal mitotic events (over 40% in treated cells, p < 0.05). Time-course studies were performed using a mouse nephrotoxicity model (cumulative 72 mg/kg). Kidneys were collected over 48 h and investigated for histopathology and DNA damage. Notable increases in γH2AX foci (indicative of double-stranded breaks) were observed in both cell culture (up to ~ 44% cells with 5+ foci at 24 h, p < 0.05) and mice treated with polymyxin B (up to ~ 25%, p < 0.05). Consistent with these results, in vitro assays showed high binding affinity of polymyxin B to DNA. Together, our results indicate that polymyxin B nephrotoxicity is associated with DNA damage, leading to chromosome missegregation and genome instability. This novel mechanistic information may lead to new strategies to overcome the nephrotoxicity of this important last-line class of antibiotics.
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What OpenQuestion holds
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.