Alveolar Epithelial Cell Injury Due to Zinc Oxide Nanoparticle Exposure
| Autor: | Kwang-Jin Kim, Ian M. Kennedy, Nazanin R. Yacobi, Farnoosh Fazlollahi, Yong Ho Kim, Edward D. Crandall, Zea Borok, Sarah F. Hamm-Alvarez |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Pulmonary and Respiratory Medicine Pathology medicine.medical_specialty Time Factors Cell Culture Techniques E. Environmental and Occupational Lung Disease Critical Care and Intensive Care Medicine medicine.disease_cause Rats Sprague-Dawley chemistry.chemical_compound Intensive care Lactate dehydrogenase Electric Impedance Animals Medicine chemistry.chemical_classification Reactive oxygen species Microscopy Confocal Dose-Response Relationship Drug L-Lactate Dehydrogenase business.industry technology industry and agriculture Epithelial Cells respiratory system Mitochondria Rats Pulmonary Alveoli Disease Models Animal Dose–response relationship chemistry Paracellular transport Toxicity Zinc toxicity Biophysics Nanoparticles Zinc Oxide Reactive Oxygen Species business Intracellular |
| Zdroj: | American Journal of Respiratory and Critical Care Medicine. 182:1398-1409 |
| ISSN: | 1535-4970 1073-449X |
| Popis: | Rationale: Although inhalation of zinc oxide (ZnO) nanoparticles (NPs) is known to cause systemic disease (i.e., metal fume fever), little is known about mechanisms underlying injury to alveolar epithelium. Objectives: Investigate ZnO NP–induced injury to alveolar epithelium by exposing primary cultured rat alveolar epithelial cell monolayers (RAECMs) to ZnO NPs. Methods: RAECMs were exposed apically to ZnO NPs or, in some experiments, to culture fluid containing ZnCl2 or free Zn released from ZnO NPs. Transepithelial electrical resistance (RT) and equivalent short-circuit current (IEQ) were assessed as functions of concentration and time. Morphologic changes, lactate dehydrogenase release, cell membrane integrity, intracellular reactive oxygen species (ROS), and mitochondrial activity were measured. Measurements and Main Results: Apical exposure to 176 μg/ml ZnO NPs decreased RT and IEQ of RAECMs by 100% over 24 hours, whereas exposure to 11 μg/ml ZnO NPs had little effect. Changes in RT and IEQ caused by 176 μg/ml ZnO NPs were irreversible. ZnO NP effects on RT yielded half-maximal concentrations of approximately 20 μg/ml. Apical exposure for 24 hours to 176 μg/ml ZnO NPs induced decreases in mitochondrial activity and increases in lactate dehydrogenase release, permeability to fluorescein sulfonic acid, increased intracellular ROS, and translocation of ZnO NPs from apical to basolateral fluid (most likely across injured cells and/or damaged paracellular pathways). Conclusions: ZnO NPs cause severe injury to RAECMs in a dose- and time-dependent manner, mediated, at least in part, by free Zn released from ZnO NPs, mitochondrial dysfunction, and increased intracellular ROS. |
| Databáze: | OpenAIRE |
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