OZONE-INDUCED PULMONARY FUNCTIONAL, PATHOLOGICAL, AND BIOCHEMICAL-CHANGES IN NORMAL AND VITAMIN-C-DEFICIENT GUINEA-PIGS

Since Vitamin C (ascorbate, AH(2)) is an important airway antioxidant and is an essential component of tissue repair, and since acute (4 hr) O-3 toxicity is enhanced by AH(2) deficiency, we hypothesized that lo nger-term O-3 effects might also be increased. Female Hartley guinea p igs (260-330 g) were fed either an AH(2)-sufficient or an AH(2)-defici ent diet 1 week prior to exposure, and were maintained on their respec tive diets during 1 week of continuous exposure to O-3 (0, 0.2, 0.4, a nd 0.8 ppm, 23 hr/day), and during 1 week postexposure recovery in cle an air. The AH(2)-deficient diet caused lung AH(2) to drop to about 30 % of control in I week, and to below 10% by the end of exposure and re covery. Body weight gains during exposure were decreased in the 0.8 pp m O-3 group, while the AH(2) deficiency began to affect body weights o nly during recovery. O-3 caused a concentration-dependent decrease in total lung capacity, vital capacity, carbon monoxide diffusing capacit y, nitrogen washout, and static compliance, while increasing forced ex piratory flow rates and residual or end-expiratory volume (suggestive of pulmonary gas-trapping). The lung/body weight ratio and fixed lung displacement volume were also increased in O-3-exposed animals. Lung p athology consisted of mononuclear cell and neutrophil infiltration, ai rway as well as alveolar epithelial cell hyperplasia, and general decr ease in epithelial cell cytoplasm. Thickening of the interstitium and an apparent increase in collagen staining were seen at the terminal br onchiolar regions. Some of these effects were marginally exacerbated i n AH(2)-deficient guinea pigs. One week postexposure to air reversed a ll O-3-induced abnormalities, irrespective of AH(2) deficiency. Whole lung hydroxyproline and desmosine were not changed at any time by eith er O-3 or AH(2) deficiency. Measurement of lung prolyl hydroxylase act ivity suggested that AH(2) deficiency as well as O-3 exposure may have increased the tissue levels of this enzyme. The lack of a significant increase in toxicity with the longer-term exposure scenario suggests that AH, has minimal influence on other compensatory mechanisms develo ped over time. (C) 1995 Society of Toxicology.