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.