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Diacetyl exposure disrupts iron homeostasis in animals and cells.

Publication ,  Journal Article
Ghio, AJ; Soukup, JM; Dailey, LA; Roggli, VL; Crumbliss, AL; Palmer, SM
Published in: Inhal Toxicol
2021

OBJECTIVE: Several mechanisms have been proposed for the biological effect of diacetyl. We tested the postulate that animal and cell exposures to diacetyl are associated with a disruption in iron homeostasis. MATERIALS AND METHODS: Male, Sprague-Dawley rats were intratracheally-instilled with either distilled water or diacetyl. Seven days after treatment, animals were euthanized and the lungs removed, fixed, and embedded. Sections were cut and stained for iron, collagen, and ferritin. Human epithelial (BEAS-2B) and monocytic (THP-1) cells were exposed in vitro to ferric ammonium citrate (FAC), diacetyl, and both FAC and diacetyl. Cell non-heme iron concentrations and ferritin levels were quantified using inductively coupled plasma optical emission spectroscopy and an immunoassay respectively. RESULTS: After exposure of animals to diacetyl, there were airway polypoid lesions which stained positively for both iron and the intracellular storage protein ferritin. Trichrome stain showed a deposition of collagen immediately adjacent to accumulated metal following diacetyl exposure. In in vitro cell exposures, FAC increased non-heme iron concentration but co-incubations of FAC and diacetyl elevated levels to significantly greater values. Levels of ferritin were increased with exposures of BEAS-2B and THP-1 cells to FAC but were similarly greater after co-exposure with FAC and diacetyl. CONCLUSIONS: Results of animal and cell studies support a disruption of iron homeostasis by diacetyl. It is proposed that, following internalization, diacetyl complexes intracellular sources of iron. The cell recognizes a loss of its requisite iron to diacetyl and imports greater concentrations of the metal.

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Published In

Inhal Toxicol

DOI

EISSN

1091-7691

Publication Date

2021

Volume

33

Issue

6-8

Start / End Page

268 / 274

Location

England

Related Subject Headings

  • Toxicology
  • THP-1 Cells
  • Rats, Sprague-Dawley
  • Rats
  • Male
  • Iron
  • Humans
  • Homeostasis
  • Diacetyl
  • Animals
 

Citation

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Ghio, A. J., Soukup, J. M., Dailey, L. A., Roggli, V. L., Crumbliss, A. L., & Palmer, S. M. (2021). Diacetyl exposure disrupts iron homeostasis in animals and cells. Inhal Toxicol, 33(6–8), 268–274. https://doi.org/10.1080/08958378.2021.1989092
Ghio, Andrew J., Joleen M. Soukup, Lisa A. Dailey, Victor L. Roggli, Alvin L. Crumbliss, and Scott M. Palmer. “Diacetyl exposure disrupts iron homeostasis in animals and cells.Inhal Toxicol 33, no. 6–8 (2021): 268–74. https://doi.org/10.1080/08958378.2021.1989092.
Ghio AJ, Soukup JM, Dailey LA, Roggli VL, Crumbliss AL, Palmer SM. Diacetyl exposure disrupts iron homeostasis in animals and cells. Inhal Toxicol. 2021;33(6–8):268–74.
Ghio, Andrew J., et al. “Diacetyl exposure disrupts iron homeostasis in animals and cells.Inhal Toxicol, vol. 33, no. 6–8, 2021, pp. 268–74. Pubmed, doi:10.1080/08958378.2021.1989092.
Ghio AJ, Soukup JM, Dailey LA, Roggli VL, Crumbliss AL, Palmer SM. Diacetyl exposure disrupts iron homeostasis in animals and cells. Inhal Toxicol. 2021;33(6–8):268–274.

Published In

Inhal Toxicol

DOI

EISSN

1091-7691

Publication Date

2021

Volume

33

Issue

6-8

Start / End Page

268 / 274

Location

England

Related Subject Headings

  • Toxicology
  • THP-1 Cells
  • Rats, Sprague-Dawley
  • Rats
  • Male
  • Iron
  • Humans
  • Homeostasis
  • Diacetyl
  • Animals