ArticleAntimicrobial agents and chemotherapy2015
Major pathways of polymyxin-induced apoptosis in rat kidney proximal tubular cells.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 71 citations in OpenAlex.
- A bibliometric analysis of polymyxin-induced nephrotoxicity research: Trends and insights (2005-2024).Medicine · 2026Article
- From Laboratory to Clinic: Translational Medicine Paradigm of Polymyxin B Nanopreparations for Overcoming Drug-Resistant Bacterial Infections.International journal of nanomedicine · 2026Review
- Molecular mechanisms attributed to colistin renal proximal tubular epithelial cytotoxicity.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2025Review
- Population Pharmacokinetic/Toxicodynamic Model for Polymyxin B in Critically Ill Patients to Identify the Risk of Nephrotoxicity.Clinical pharmacology and therapeutics · 2025Observational
- Zileuton Attenuates Acute Kidney Injury in Glycerol-Induced Rhabdomyolysis by Regulating Myeloid-Derived Suppressor Cells in Mice.International journal of molecular sciences · 2025Article
- Corynoxeine Supplementation Ameliorates Colistin-Induced Kidney Oxidative Stress and Inflammation in Mice.Antioxidants (Basel, Switzerland) · 2025Article
- The physiological characteristics of inward rectifying potassium channel Kir4.2 and its research progress in human diseases.Frontiers in cell and developmental biology · 2025Review
- Evaluating nephrotoxicity reduction in a novel polymyxin B formulation: insights from a 3D kidney-on-a-chip model.Antimicrobial agents and chemotherapy · 2024Article
- Preliminary Investigation of Side Effects of Polymyxin B Administration in Hospitalized Horses.Antibiotics (Basel, Switzerland) · 2023Article
- Synchrotron-based X-ray fluorescence microscopy reveals accumulation of polymyxins in single human alveolar epithelial cells.Antimicrobial agents and chemotherapy · 2023Article
- Targeted Desorption Electrospray Ionization Mass Spectrometry Imaging for Drug Distribution, Toxicity, and Tissue Classification Studies.Metabolites · 2023Article
- Transcriptomic Responses to Polymyxin B and Analogues in Human Kidney Tubular Cells.Antibiotics (Basel, Switzerland) · 2023Article
- Adverse effects of polymyxin B administration to healthy horses.Journal of veterinary internal medicine · 2022Article
- Urinary Metabolomics From a Dose-Fractionated Polymyxin B Rat Model of Acute Kidney Injury.International journal of antimicrobial agents · 2022Article
- Genome-scale metabolic modeling in antimicrobial pharmacology.Engineering microbiology · 2022Review
- Inwardly rectifying potassium channels mediate polymyxin-induced nephrotoxicity.Cellular and molecular life sciences : CMLS · 2022Article
- Pharmacokinetics and pharmacodynamics of peptide antibiotics.Advanced drug delivery reviews · 2022Review
- A synthetic lipopeptide targeting top-priority multidrug-resistant Gram-negative pathogens.Nature communications · 2022Article
- Polymyxin B-Based Regimens for Patients Infected with Carbapenem-Resistant Gram-Negative Bacteria: Clinical and Microbiological Efficacy, Mortality, and Safety.Infection and drug resistance · 2022Article
- Polymyxin-Induced Metabolic Perturbations in Human Lung Epithelial Cells.Antimicrobial agents and chemotherapy · 2021Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Identifying the pathways involved in the apoptotic cell death that is associated with polymyxin-induced nephrotoxicity is crucial for the development of strategies to ameliorate this dose-limiting side effect and for the development of novel safer polymyxins. The primary aim of this study was to identify the major pathways which lead to polymyxin-induced apoptosis in cultured rat kidney proximal tubular cells (NRK-52E). Caspase-3, -8, and -9 were activated by polymyxin B treatment in a concentration-dependent manner. Concentration- and time-dependent expression of FasL and deformation of mitochondrial morphology were revealed following polymyxin B treatment. The proportion of cells with filamentous mitochondria (regular morphology) following an 8-h treatment with 1.0 mM polymyxin B was 56.2% ± 9.7% (n = 3). This was decreased to 30.7% ± 7.5% when the polymyxin B concentration was increased to 2.0 mM. The mitochondrial membrane potential (Δψm) decreased to 14.1% ± 2.9% in the cells treated with 1.0 mM polymyxin B for 24 h (n = 3) compared to that in the untreated control group. Concomitantly, concentration- and time-dependent production of mitochondrial superoxide was also observed. This study is the first to have demonstrated that polymyxin-induced apoptosis is mediated through both the death receptor and mitochondrial pathways in cultured renal tubular cells. It provides key information not only for the amelioration of polymyxin-induced nephrotoxicity but also for the discovery of novel safer polymyxin-like antibiotics against Gram-negative "superbugs."
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