Diacetyl increases sensory innervation and substance P production in rat trachea

Details

• Personal Author:
  Battelli LA ; Cumpston A ; Dey RD ; Fedan, Jeffery S. ; Frazer DG ; Goldsmith WT ; Goravanahally MP ; Hubbs, Ann F. ; Jackson MC ; Kashon ML ; Mercer RR
• Description:
  Vapors of butter flavor often contain diacetyl, an alpha-diketone that imparts the aroma and flavor of butter. Diacetyl causes epithelial necrosis and inflammation in rat and mouse airways. Diacetyl-exposed workers can develop fixed airway obstruction, but some exposed workers have symptoms of other conditions including self-reported wheezing. Pharmacokinetic modeling indicates that, at given vapor concentrations, the rat trachea receives comparable doses to human intrapulmonary airways following diacetyl inhalation. Substance P (SP) in sensory neurons plays a critical role in airway hyperresponsiveness and inflammation. Therefore, we investigated the hypothesis that diacetyl inhalation alters sensory innervation and SP production in airway epithelium. Neurons in jugular and nodose ganglia projecting to the airways were retrogradely labeled by tracheal instillation of rhodamine microspheres. Rats (6/group) were exposed to 0, 25, 249, or 346 ppm diacetyl for 6 h. One day post-exposure, ganglia and upper trachea were processed for SP immunofluorescence. SP immunoreactive sensory nerve fibers and cell bodies were measured by morphometry. Diacetyl inhalation caused a dose-dependent increase in the number of SP immunoreactive airway neurons in jugular ganglia from 3.26 +/- 3.0 (control) to 14.70 +/- 5.9, 22.70 +/- 8.4, and 25.5 +/- 6.6 at 25, 249 and 346 ppm, respectively. In trachea, after inhaling 346 ppm diacetyl, sensory nerve fiber density was unchanged in the fields with intact epithelium. However, the innervation was significantly increased in the intact epithelium adjacent to denuded foci (5.7 fold) and in foci with detaching epithelium (3.3 fold). These findings suggest that acute diacetyl inhalation causes dose-dependent SP production in airway neurons of jugular ganglia and increased epithelial innervation in tracheal foci with specific types of epithelial injury. [Description provided by NIOSH]
• Subjects:
  Animals Food Additives Laboratories Lung Nervous System Occupational Health Respiratory System Safety
• Keywords:
  Animal-studies Food-additives Laboratory-animals Nerve-fibers Nerve-tissue Nerves Nervous-system-function Pulmonary-system
• ISSN:
  0300-9858
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  47
• Issue:
  6
• NIOSHTIC Number:
  nn:20037759
• Citation:
  Vet Pathol 2010 Nov; 47(6)(Suppl):56S
• CAS Registry Number:
  Butanedione (CAS RN 431-03-8)
• Federal Fiscal Year:
  2011
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  Veterinary Pathology
• Supplement:
  Suppl
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:a60e86cac80103a3bc1432719b7dd3b23cc3fb707d41909fd35cd86bc63038931d6c4c1dfd7c0da2d687cb86c01219bcfb29bb462c0eeffe928539a125059e69
• Download URL:
  https://stacks.cdc.gov/view/cdc/191744/cdc_191744_DS1.pdf
• File Type:
  [PDF - 289.81 KB ]