Influence of age on the biochemical response of rat lung to ozone exposure

We have previously examined the influence of animal age on the pulmonary response to ozone (O3) in rats between 7 and 90 days of age (Elsayed et al., 1982a). In the present study, we expanded the age groups of rats, and examined in greater detail the relationship between animal age and pulmonary response to inhaled O3. We exposed 7 groups of specific pathogen free, male Sprague-Dawley rats, aged 24, 30, 45, 60, 90, 180, and 365 days, to 0.8 ppm (1568 micrograms/m3) O3 continuously for 3 days. After O3 exposure, we sacrificed the exposed rats and a matched number of controls from each age group, and analyzed their lungs for a series of physical and biochemical parameters, including glutathione metabolizing and NADPH producing enzyme activities. We observed that in control rats all the parameters increased as a function of age. However, the rate of increase was generally slower after age 60 days. After O3 exposure there was an increase in all the parameters for all age groups relative to their corresponding controls, but the extent of increase was significantly larger in rats 60 days and older than in younger rats. A regression of the difference in mean values between control and exposed animals for each parameter against age showed a linear correlation, indicating that the response was age-dependent. Since the magnitude of such increases is thought to reflect the degree of lung injury, the results suggest that O3 exposure causes greater lung injury in older rats than in younger rats. We tested this assumption by exposing rats from four different age groups (24, 45, 60 and 90 days) to a lethal dose of O3 (4 ppm or 7840 micrograms/m3 for 8 hours). The mortality rates were 50% and 83% for 24 and 45 day old rats, respectively, and 100% for 60 and 90 day old rats. The results of these studies further demonstrate that older rats are more susceptible to lung injury from O3 than younger rats.