API

Event: 1586

Key Event Title

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Airway epithelial injury

Short name

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Airway epithelial injury

Biological Context

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Level of Biological Organization
Cellular

Cell term

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Organ term

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Key Event Components

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Process Object Action

Key Event Overview


AOPs Including This Key Event

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AOP Name Role of event in AOP
α-diketone-induced bronchiolitis obliterans KeyEvent

Stressors

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Taxonomic Applicability

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Life Stages

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Sex Applicability

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Key Event Description

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Inhalation of to low concentrations of α-diketones generally does not result in airway injury. However, above a certain threshold the airway epithelium becomes persistently damaged.


How It Is Measured or Detected

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Histopathological abnormalities in exposed rats, airway epithelial necrosis, flattening of the airway epithelial cells, loss of cilia (Foster et al. 2017), gaps in the epithelial layer (Hubbs et al. 2002, 2008). Also a reduced expression of club cell secretory protein in airway epithelium has been observed after a-diketone exposure (Palmer et al. 2011). Within in vitro models of airway epithelium, the loss of epithelial barrier function following exposure can be measured as a reduction in transepithelial electrical resistance (TEER, Fedan et al. 2006, Zaccone et al 2015)


Domain of Applicability

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References

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Foster, M. W., Gwinn, W. M., Kelly, F. L., Brass, D. M., Valente, A. M., Moseley, M. A., … Palmer, S. M. (2017). Proteomic Analysis of Primary Human Airway Epithelial Cells Exposed to the Respiratory Toxicant Diacetyl. Journal of Proteome Research, 16(2), 538–549. https://doi.org/10.1021/acs.jproteome.6b00672

Hubbs, A. F., Goldsmith, W. T., Kashon, M. L., Frazer, D., Mercer, R. R., Battelli, L. A., … Castranova, V. (2008). Respiratory Toxicologic Pathology of Inhaled Diacetyl in Sprague-Dawley Rats. Toxicologic Pathology, 36(2), 330–344. https://doi.org/10.1177/0192623307312694

Palmer, S. M., Flake, G. P., Kelly, F. L., Zhang, H. L., Nugent, J. L., Kirby, P. J., … Morgan, D. L. (2011). Severe airway epithelial injury, aberrant repair and Bronchiolitis obliterans develops after diacetyl instillation in rats. PLoS ONE, 6(3). https://doi.org/10.1371/journal.pone.0017644

Zaccone, E. J., Goldsmith, W. T., Shimko, M. J., Wells, J. R., Schwegler-Berry, D., Willard, P. A., … Fedan, J. S. (2015). Diacetyl and 2,3-pentanedione exposure of human cultured airway epithelial cells: Ion transport effects and metabolism of butter flavoring agents. Toxicology and Applied Pharmacology, 289, 542–549. https://doi.org/10.1016/j.taap.2015.10.004