Episodic ozone exposure over two weeks alters pulmonary inflammation and gene expression in Long-Evans rats.
Objective: Ozone exposure often occurs episodically over short windows of time. However, laboratory investigations have consistently reported that repeated exposure to ozone produces an adaptation response. With this in mind, we sought to develop a rodent model of episodic ozone exposure and characterize the impacts of this paradigm on typical pulmonary toxicity endpoints.
Methods: Male, Long-Evans rats were exposed to either 2-days or 2-weeks of episodic exposure to filtered air, 0.4 ppm, or 0.8 ppm ozone (4 hours / day). Rats in the 2-week group were exposed to one- to-two-days of consecutive exposures followed by one- to-four-day breaks between each episode. Whole body plethysmography was performed following each exposure. All groups were euthanized ~24 hours after the final exposure to measure markers of lung injury and inflammation in the bronchoalveolar lavage fluid, as well as qPCR in the lung tissue for select genes.
Results: The effects of ozone inhalation on breathing parameters and pulmonary leakage were lost with consecutive episodes of exposure. Increased immune cell infiltration and cytokines were present to the same extent in the 2-week group as observed in the 2-day group. Furthermore, the expression of genes involved in neuroendocrine signaling was more greatly impacted at 2-weeks compared to 2-days of exposure.
Conclusions: Aspects of the adaptation response were still present in rats episodically exposed to ozone over two weeks. On the other hand, ozone-mediated alterations in pulmonary immune populations show continued responsiveness in this model, suggesting that adaptation may be endpoint specific.