Age-Related Toxicity in Rat Lungs Following Acute and Repeated Ozone Exposure

Abstract

The evidence is inconclusive as to whether age and gender are important determinants of ozone toxicity We carried out an experiment to investigate the possible age- and gender-related differences in pulmonary toxicity following both acute and repeated exposure to ozone. Male and female rats of various ages (1, 3, 9, and 18 mo) were exposed to 0.8 mg O₃/m³ for 1 day (12 h) or for 7 days (12 h/day) during the dark period. Bronchoalveolar lavage (BAL) and biochemical, histopathological, and immunological techniques were used to determine the permeability, antioxidant capacity, tissue morphology, and extent of inflammation in the lungs. Morphological as well as morphometric results showed age-related differences in the extent of pulmonary lesions after 1 and 7 days of ozone exposure; from the age of 3 mo animals became less susceptible to ozone. Pulmonary antioxidant enzyme capacity in control rats appeared to exhibit an age-related decline starting at 3 mo. However, exposure to ozone resulted in an increase in enzyme activities in rats aged 9 and 18 mo. There was no significant overall age-related effect of ozone. However, a different pattern existed between both sexes in their age-related reaction to ozone exposure. The percentage increase of protein and albumin concentrations in BAL increased after acute ozone exposure, peaking at the age of 1 mo. The lesser increase at the age of 9 and 18 mo suggests a decreasing sensitivity in older rats. The gradual decrease of the net percentage of polymorphonuclear leukocytes (PMNs) in BAL after ozone exposure in male rats with age corroborates this suggestion. Ozone exposure decreased the clearance of Listeria bacteria in lungs. There was no significant difference between the various age groups in the resistance to Listeria infection after ozone exposure. It can therefore be concluded that specific toxicity indices including lung tissue damage, increased permeability, and inflammation point to a more pronounced responsiveness of younger animals to ozone. No gender-related differences in the response to ozone were observed for any of the parameters examined. These data support the view that age is a significant predictor of the pulmonary response to ozone, with younger subjects being more sensitive.