Rat lung recovery from 3 days of continuous exposure to 0.75 ppm ozone

Abstract

The present study investigated the inflammatory responses and enzyme levels in lungs isolated from male Wistar rats after 3 d of continuous exposure to 0.75 ppm ozone and following 4 d of recovery in air. These times are associated with maximal proliferation of the alveolar type II epithelium and their subsequent transformation to new type I cells. Immediately following ozone exposure, bronchoalveolar lavage demonstrated neutrophil accumulation that was no longer present 4 d later. The number of lavaged macrophages was also found to be increased immediately following ozone exposure, and remained elevated at 4 d postexposure. Whole-lung determinations of key enzymes involved in energy generation (succinate oxidase) and maintenance of lung NADPH and reduced glutathione were corrected for changes in cell number, by use of lung DNA measurements. Immediately following ozone exposure succinate oxidase (SOX), glucose-6-phosphate (G6PD), and 6-phosphogluconate (6PGD) dehydrogenase activities per milligram DNA were significantly enhanced by 76%, 48%, and 21%, respectively. These data suggested that ozone-exposed lungs had cells with increased mitochondria and NADPH-generating capability consistent with the increased metabolic needs of a proliferating epithelium. At 4 d postexposure, only G6PD activity per milligram DNA remained higher by 22% than air-exposed controls. Although both glutathione reductase (GSSG-R) and peroxidase (GSH-Px) activities per lung were elevated in lungs immediately following exposure and 4 d later, when corrected for DNA only GSH-Px activity was significantly increased by 29% in lungs after the postexposure period. Lungs 4 d postexposure therefore had cells relatively enriched in G6PD and GSH-Px that might account for the increased ozone tolerance that has previously been associated with the formation of new type I epithelium.