Age-related differences in pulmonary effects of acute and subchronic episodic ozone exposures in Brown Norway rats

Abstract

Ozone (O₃) is known to induce adverse pulmonary and systemic health effects. Importantly, children and older persons are considered at-risk populations for O₃-induced dysfunction, yet the mechanisms accounting for the age-related pulmonary responses to O₃ are uncertain. In this study, we examined age-related susceptibility to O₃ using 1 mo (adolescent), 4 mo (young adult), 12 mo (adult) and 24 mo (senescent) male Brown Norway rats exposed to filtered air or O₃ (0.25 and 1.00 ppm), 6 h/day, two days/week for 1 week (acute) or 13 weeks (subchronic). Ventilatory function, assessed by whole-body plethysmography, and bronchoalveolar lavage fluid (BALF) biomarkers of injury and inflammation were used to examine O₃-induced pulmonary effects. Relaxation time declined in all ages following the weekly exposures; however, this effect persisted only in the 24 mo rats following a five days recovery, demonstrating an inability to induce adaptation commonly seen with repeated O₃ exposures. PenH was increased in all groups with an augmented response in the 4 mo rats following the subchronic O₃ exposures. O₃ led to increased breathing frequency and minute volume in the 1 and 4 mo animals. Markers of pulmonary permeability were increased in all age groups. Elevations in BALF γ-glutamyl transferase activity and lung inflammation following an acute O₃ exposure were noted in only the 1 and 4 mo rats, which likely received an increased effective O₃ dose. These data demonstrate that adolescent and young adult animals are more susceptible to changes in ventilation and pulmonary injury/inflammation caused by acute and episodic O₃ exposure.

• Adaptation
• age-related susceptibility
• ozone
• pulmonary
• whole-body plethysmography

Acknowledgements

The authors would like to thank Drs. Marie McGee, Jan Dye and Michael Madden of the US EPA for their critical review of this manuscript, and Mr. Dock Terrell for providing technical assistance in the operation of the exposure system.

Declaration of interest

SJS and VLB are Oak Ridge Institute for Science and Education Fellows. The authors report no declarations of interest.

The research described in this article has been reviewed by the National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency and approved for publication. Approval does not signify that the contents necessarily reflect the views and the policies of the Agency, nor does mention of trade names of commercial products constitute endorsement or recommendation for use.