API

Event: 1587

Key Event Title

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Fibroproliferative airway lesions

Short name

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Fibroproliferative airway lesions

Biological Context

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Level of Biological Organization
Tissue


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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Repeated exposure to α-diketones might result in the loss of the regenerative capacity of the airway epithelium, e.g. due to insufficient residual stem cells. Sustained loss of the epithelial cells might lead to damage to the underlying basement membrane and exposure of the lamina propria. Fibroblast in the lamina propria are activated and start to proliferate and elaborate collagen matrix. Cytokines and growth factors released by epithelial cells and infiltrated neutrophils may promote the migration and proliferation of fibroblasts into the airway lumen. The initially fibromyxoid tissue is gradually replaced by mature connective tissue that is rich in collagen (rats, Flake & Morgan 2017).


How It Is Measured or Detected

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Fibroproliferative airway lesions can be observed in biopsies of α-diketone exposed laboratory animals in a dose dependent manner using various tissue stainings of histological specimen. (rats, Morgan et al. 2016, Flake & Morgan 2017)


Domain of Applicability

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References

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Flake, G. P., & Morgan, D. L. (2017). Pathology of diacetyl and 2,3-pentanedione airway lesions in a rat model of obliterative bronchiolitis. Toxicology, 388, 40–47. https://doi.org/10.1016/j.tox.2016.10.013

Morgan, D. L., Jokinen, M. P., Johnson, C. L., Price, H. C., Gwinn, W. M., Bousquet, R. W., & Flake, G. P. (2016). Chemical Reactivity and Respiratory Toxicity of the alpha-Diketone Flavoring Agents: 2,3-Butanedione, 2,3-Pentanedione, and 2,3-Hexanedione. Toxicologic Pathology, 44(5), 763–783. https://doi.org/10.1177/0192623316638962