OZONE-INDUCED TISSUE-INJURY AND CHANGES IN ANTIOXIDANT HOMEOSTASIS IN NORMAL AND ASCORBATE-DEFICIENT GUINEA-PIGS

It has been reported previously that ozone (O-3) toxicity from acute (4 hr) exposure is enhanced by ascorbate (AH(2)) deficiency in guinea pigs. We hypothesized that lung injury from continuous 1-week O-3 exposure would also be increased under conditions of AH(2) deficiency because of (1) a diminished antioxidant pool to counteract the oxidant challenge, (2) impaired reparation of tissue injury, and/or (3) altered antioxidant redox homeostasis. Female Hartley guinea pigs (260-330 g) were made AH(2) deficient by providing a diet similar to guinea pig chow, but having no AH(2). The dietary regimen was started 1 week prior to exposure and was continued during exposure to O-3 (0, 0 2, 0.4, or 0.8 ppm, 23 hr/day, 7 days) as well as 1 week post-exposure. Bronchoalveolar lavage (BAL) and tissue AH(2) were measured in subgroups at the beginning of exposure (1 week on the AH(2)-deficient diet), at its termination and 1 week post-exposure. AH(2) measured in ear tissue punches proved to be an easy and effective monitor for AH(2) deficiency. One week on the AH,-deficient diet caused a 70-80% drop in ear, lung and liver AH(2), while AH(2) in BAL was decreased by 90%. Immediately after the exposure, total BAL protein and albumin (markers of lung permeability) were increased (similar to 50%) at 0.8 ppm with no difference between the dietary groups. O-3 caused an increase in total BAL cells and neutrophils in a concentration-dependent manner with only a slight augmentation due to diet. Exposure to O-3 caused an increase in lung and BAL AH(2) in normal guinea pigs. Glutathione and uric acid were also increased in the lung and BAL after O-3 exposure (40-570%) in both dietary groups, and the levels remained elevated during the recovery period. Lung alpha-tocopherol was not changed due to O-3. A significant overall diet-related decrease was seen in AH(2)-deficient guinea pigs, immediately after the exposure and recovery. In summary, lung injury/inflammation following 1 week O-3 exposure and recovery were minimally affected by AH(2) deficiency. Antioxidants also appeared to increase in response to O-3 exposure despite the deficiency in AH(2).