Respiratory and olfactory cytotoxicity of inhaled 2,3-pentanedione in Sprague-Dawley rats.

Abstract

Flavorings-related lung disease is a potentially disabling disease of food industry workers associated with exposure to the α-diketone butter flavoring, diacetyl (2,3-butanedione). To investigate the hypothesis that another α-diketone flavoring, 2,3-pentanedione, would cause airway damage, rats that inhaled air, 2,3-pentanedione (112, 241, 318, or 354 ppm), or diacetyl (240 ppm) for 6 hours were sacrificed the following day. Rats inhaling 2,3-pentanedione developed necrotizing rhinitis, tracheitis, and bronchitis comparable to diacetyl-induced injury. To investigate delayed toxicity, additional rats inhaled 318 (range, 317.9-318.9) ppm 2,3-pentanedione for 6 hours and were sacrificed 0 to 2, 12 to 14, or 18 to 20 hours after exposure. Respiratory epithelial injury in the upper nose involved both apoptosis and necrosis, which progressed through 12 to 14 hours after exposure. Olfactory neuroepithelial injury included loss of olfactory neurons that showed reduced expression of the 2,3-pentanedione-metabolizing enzyme, dicarbonyl/L-xylulose reductase, relative to sustentacular cells. Caspase 3 activation occasionally involved olfactory nerve bundles that synapse in the olfactory bulb (OB). An additional group of rats inhaling 270 ppm 2,3-pentanedione for 6 hours 41 minutes showed increased expression of IL-6 and nitric oxide synthase-2 and decreased expression of vascular endothelial growth factor A in the OB, striatum, hippocampus, and cerebellum using real-time PCR. Claudin-1 expression increased in the OB and striatum. We conclude that 2,3-pentanedione is a respiratory hazard that can also alter gene expression in the brain.

• Authors: Ann F Hubbs, Amy M Cumpston, W Travis Goldsmith, Lori A Battelli, Michael L Kashon, Mark C Jackson, David G Frazer, Jeffrey S Fedan, Madhusudan P Goravanahally, Vincent Castranova, Kathleen Kreiss, Patsy A Willard, Sherri Friend, Diane Schwegler-Berry, Kara L Fluharty, Krishnan Sriram
• Journal: The American journal of pathology (Am J Pathol) Vol. 181 Issue 3 Pg. 829-44 (Sep 2012) ISSN: 1525-2191 [Electronic] United States
• PMID: 22894831 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
• Copyright: Published by Elsevier Inc.

Chemical References

• Cadherins
• Olfactory Marker Protein
• Pentanones
• RNA, Messenger
• Sugar Alcohol Dehydrogenases
• L-xylulose reductase
• Caspase 3
• Diacetyl
• 2,3-pentanedione

Topics

• Administration, Inhalation
• Animals
• Cadherins (metabolism)
• Caspase 3 (metabolism)
• Cell Death (drug effects)
• Diacetyl (toxicity)
• Epithelium (drug effects, pathology)
• Fluorescent Antibody Technique
• Gene Expression Regulation (drug effects)
• Male
• Neurons (drug effects, pathology)
• Olfactory Bulb (drug effects, pathology)
• Olfactory Marker Protein (metabolism)
• Pentanones (administration & dosage, toxicity)
• RNA, Messenger (genetics, metabolism)
• Rats
• Rats, Sprague-Dawley
• Reproducibility of Results
• Respiratory System (pathology)
• Staining and Labeling
• Sugar Alcohol Dehydrogenases (metabolism)
• Time Factors