ArticleAntimicrobial agents and chemotherapy2017
Potential Toxicity of Polymyxins in Human Lung Epithelial Cells.
Article in Antimicrobial agents and chemotherapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 45 citations in OpenAlex.
- Nanoemulsion-based colistin for pulmonary delivery: Enhanced antibacterial efficacy against Acinetobacter baumannii.Drug delivery and translational research · 2026Article
- Iturin A disruptsNpj fungal science · 2026Article
- Population pharmacokinetics study on nebulized and intravenous administration of polymyxin B in patients with pneumonia caused by multidrug-resistant gram-negative bacteria.Antimicrobial agents and chemotherapy · 2025Article
- Aerosolized delivery resulting in high polymyxin B concentration levels in epithelial lining fluid ensures efficacy in ventilator-associated pneumonia.JAC-antimicrobial resistance · 2025Article
- Polymyxin B Peptide Hydrogel Coating: A Novel Approach to Prevent Ventilator-Associated Pneumonia.International journal of molecular sciences · 2024Article
- Dextrin conjugation to colistin inhibits its toxicity, cellular uptake and acute kidney injuryRSC pharmaceutics · 2024Article
- Tobramycin Reduces Pulmonary Toxicity of Polymyxin B via Inhibiting the Megalin-Mediated Drug Uptake in the Human Lung Epithelial Cells.Pharmaceutics · 2024Article
- Synchrotron-based X-ray fluorescence microscopy reveals accumulation of polymyxins in single human alveolar epithelial cells.Antimicrobial agents and chemotherapy · 2023Article
- Improved Aerosolization Stability of Inhalable Tobramycin Powder Formulation by Co-Spray Drying with Colistin.Pharmaceutical research · 2022Article
- 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
- Polymyxin Induces Significant Transcriptomic Perturbations of Cellular Signalling Networks in Human Lung Epithelial Cells.Antibiotics (Basel, Switzerland) · 2022Article
- An Efficient Approach for the Design and Synthesis of Antimicrobial Peptide-Peptide Nucleic Acid Conjugates.Frontiers in chemistry · 2022Article
- Polymyxin-Induced Metabolic Perturbations in Human Lung Epithelial Cells.Antimicrobial agents and chemotherapy · 2021Article
- Repurposing of the Fasciolicide Triclabendazole to Treat Infections Caused byMicroorganisms · 2021Article
- Rescuing the Last-Line Polymyxins: Achievements and Challenges.Pharmacological reviews · 2021Review
- In vitro evaluation of drug delivery behavior for inhalable amorphous nanoparticle formulations in a human lung epithelial cell model.International journal of pharmaceutics · 2021Article
- The Difference Between Polymyxin B and Polymyxin E in Causing Skin Hyerpigmentation.Frontiers in pharmacology · 2021Article
- Treatment of infections caused by Gram-negative pathogens: current status on the pharmacokinetics/pharmacodynamics of parenteral and inhaled polymyxins in patients.International journal of antimicrobial agents · 2020Review
- Polymyxin B-induced rhabdomyolysis: A case report.Medicine · 2020Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Inhaled polymyxins are of considerable utility in achieving optimal exposure in the respiratory tract for the treatment of lung infections caused by multidrug-resistant Gram-negative pathogens. Current inhaled polymyxin therapy is empirical, and often large doses are used that may lead to potential pulmonary adverse effects. This study aimed to investigate the effect of polymyxins on human lung epithelial (A549) cells. The viability of A549 cells was examined after treatment with polymyxins by flow cytometry. Activation of caspases 3, 8, and 9, expression of Fas ligand (FasL), loss of mitochondrial membrane potential, and mitochondrial oxidative stress induced by polymyxin B were evaluated. The concentration of polymyxin B required to induce 50% of maximal cell death was 1.74 mM (95% confidence interval, 1.60 to 1.90 mM). Colistin was at least 2-fold less toxic than polymyxin B, while colistimethate was nontoxic. With 2.0 mM polymyxin B, 30.6% ± 11.5% (mean ± standard deviation) of the cells were apoptotic at 8 h and this increased to 71.3% ± 3.72% at 24 h. Concentration- and time-dependent activation of caspases 3, 8, and 9 was evident, while the activation of caspase 9 was more dramatic. Furthermore, polymyxin B caused concentration- and time-dependent FasL expression, production of mitochondrial reactive oxygen species, and changes in mitochondrial membrane potential. This is the first study to demonstrate that both extrinsic death receptor and intrinsic mitochondrial pathways are involved in polymyxin-induced toxicity in A549 cells. This knowledge base is critical for the development of novel strategies for the safe and effective inhalation therapy of polymyxins against Gram-negative "superbugs."
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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.