The role of inflammatory mediators in the synergistic toxicity of ozone and 1-nitronaphthalene in rat airways

Kara R. Schmelzer, Åsa M. Wheelock, Katja Dettmer, Dexter Morin, Bruce D. Hammock

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Ambient air is polluted with a mixture of pulmonary toxicants. Previous studies indicate that prior exposure to atmospheric oxidant pollutants such as ozone may significantly alter the response to other pollutants, such as 1-nitronaphthalene (1-NN). 1-NN, a component of the particulate exhaust from diesel engines, has been found at low concentrations in ambient air. Using a metabolomic approach, we investigated inflammatory responses in arachidonic and linoleic acid biochemical cascades (35 metabolites) and the expression of 19 cytokines/chemokines at three time points (2, 6, and 24 hr) following exposure to 1-NN with and without prior long-term 03 exposure. Long-term 03 exposure is associated with biochemical changes that have been shown to tender the lung resistant to further 03 exposure. This study indicates that airways of 03-tolerant rats exhibited a low level of chronic inflammation, rendering the lungs more susceptible to other environmental pollutants such as 1-NN. Specifically, a 12.5-mg/kg dose of 1-NN to 03-tolerant rats produced significantly higher levels of cysteinyl-leukotrienes in bronchiolar lavage fluid even when compared to a 50-mg/kg close of 1-NN in rats exposed to filtered air. Collectively, these results indicate that the combination of exposures as encountered in polluted ambient air are considerably more injurious to the lung than would be anticipated from previous studies employing single exposures. The observed synergism between 03 and 1-NN may be causally related to a shift in a T-helper 1 to T-helper 2 immune response in the airways.

Original languageEnglish (US)
Pages (from-to)1354-1360
Number of pages7
JournalEnvironmental Health Perspectives
Issue number9
StatePublished - Sep 2006


  • 1-nitronaphthalene
  • Arachidonic acid
  • Cyclooxygenase
  • Inflammatory mediators
  • Linoleic acid
  • Lipoxygenase
  • Ozone

ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry
  • Public Health, Environmental and Occupational Health


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