© 1995 Oxford University Press
research-article |
Ozone-Induced Pulmonary Functional, Pathological, and Biochemical Changes in Normal and Vitamin C-Deficient Guinea Pigs1
*Center for Environmental Medicine and Lung Biology, University of North Carolina Chapel Hill, North Carolina 27599-7310
Pulmonary Toxicology Branch. Health Effects Research Laboratories, U S. Environmental Protection Agency, Research Triangle Park North Carolina 27711
Department of Biochemistry. The University of Texas Health Center at Tyler Tyler, Texas 75710
§Department of Veterinary Molecular Biosciences. School of Veterinary Medicine. University of California at Davis California 95616
¶Mantech Environmental Technology Inc., Research Triangle Park North Carolina 27709
Received February 15, 1994; accepted July 11, 1994
Since Vitamin C (ascorbate, AH2) is an important airway antioxidant and is an essential component of tissue repair, and since acute (4 hr) O3 toxicity is enhanced by AH2 deficiency, we hypothesized that longer-term O3 effects might also be increased. Female Hartley guinea pigs (260–330 g) were fed either an AH2-sufficient or an AH2-deficient diet 1 week prior to exposure, and were maintained on their respective diets during 1 week of continuous exposure to O3 (0, 0.2, 0.4, and 0.8 ppm, 23 hr/day), and during 1 week postexposure recovery in clean air. The AH2-deficient diet caused lung AH2 to drop to about 30% of control in 1 week, and to below 10% by the end of exposure and recovery. Body weight gains during exposure were decreased in the 0.8 ppm O3 group, while the AH2 deficiency began to affect body weights only during recovery. O3 caused a concentration-dependent decrease in total lung capacity, vital capacity, carbon monoxide diffusing capacity, nitrogen washout, and static compliance, while increasing forced expiratory 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 O3-exposed animals. Lung pathology consisted of mononuclear cell and neutrophil infiltration, airway as well as alveolar epithelial cell hyperplasia, and general decrease in epithelial cell cytoplasm.
Thickening of the interstitium and an apparent increase in collagen staining were seen at the terminal bronchiolar regions. Some of these effects were marginally exacerbated in AH2-defi- cient guinea pigs. One week postexposure to air reversed all O3-induced abnormalities, irrespective of AH2 deficiency. Whole lung hydroxyproline and desmosine were not changed at any time by either 03 or AH2 deficiency. Measurement of lung prolyl hydroxylase activity suggested that AH2 deficiency as well as 03 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 AH2 has minimal influence on other compensatory mechanisms developed over time.