Kodavanti U P, Costa D L, Dreher K L, Crissman K, Hatch G E
Pulmonary Toxicology Branch, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Biochem Pharmacol. 1995 Jul 17;50(2):243-51. doi: 10.1016/0006-2952(95)00122-g.
It has been reported previously that ozone (O3) toxicity from acute (4 hr) exposure is enhanced by ascorbate (AH2) deficiency in guinea pigs. We hypothesized that lung injury from continuous 1-week O3 exposure would also be increased under conditions of AH2 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 AH2 deficient by providing a diet similar to guinea pig chow, but having no AH2. The dietary regimen was started 1 week prior to exposure and was continued during exposure to O3 (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 AH2 were measured in subgroups at the beginning of exposure (1 week on the AH2-deficient diet), at its termination and 1 week post-exposure. AH2 measured in ear tissue punches proved to be an easy and effective monitor for AH2 deficiency. One week on the AH2-deficient diet caused a 70-80% drop in ear, lung and liver AH2, while AH2 in BAL was decreased by 90%. Immediately after the exposure, total BAL protein and albumin (markers of lung permeability) were increased (approximately 50%) at 0.8 ppm with no difference between the dietary groups. O3 caused an increase in total BAL cells and neutrophils in a concentration-dependent manner with only a slight augmentation due to diet. Exposure to O3 caused an increase in lung and BAL AH2 in normal guinea pigs. Glutathione and uric acid were also increased in the lung and BAL after O3 exposure (40-570%) in both dietary groups, and the levels remained elevated during the recovery period. Lung alpha-tocopherol was not changed due to O3. A significant overall diet-related decrease was seen in AH2-deficient guinea pigs, immediately after the exposure and recovery. In summary, lung injury/inflammation following 1 week O3 exposure and recovery were minimally affected by AH2 deficiency. Antioxidants also appeared to increase in response to O3 exposure despite the deficiency in AH2.
先前已有报道称，豚鼠急性（4小时）暴露于臭氧（O3）时，抗坏血酸盐（AH2）缺乏会增强O3毒性。我们推测，在AH2缺乏的情况下，连续1周暴露于O3引起的肺损伤也会增加，原因如下：（1）抗氧化剂储备减少，无法应对氧化剂的挑战；（2）组织损伤修复受损；和/或（3）抗氧化剂氧化还原稳态改变。通过提供一种类似于豚鼠饲料但不含AH2的饮食，使雌性Hartley豚鼠（260 - 330克）缺乏AH2。饮食方案在暴露前1周开始，并在暴露于O3期间（0、0.2、0.4或0.8 ppm，每天23小时，共7天）以及暴露后1周持续进行。在暴露开始时（食用AH2缺乏饮食1周）、暴露结束时和暴露后1周，对亚组动物进行支气管肺泡灌洗（BAL）和组织AH2测量。经证明，在耳部组织打孔处测量AH2是一种简单有效的监测AH2缺乏的方法。食用AH2缺乏饮食1周后，耳部、肺部和肝脏的AH2下降了70 - 80%，而BAL中的AH2下降了90%。暴露后立即发现，在0.8 ppm时，总BAL蛋白和白蛋白（肺通透性标志物）增加（约50%），不同饮食组之间无差异。O3以浓度依赖的方式导致总BAL细胞和中性粒细胞增加，饮食造成的影响较小。暴露于O3会使正常豚鼠的肺部和BAL中的AH2增加。在两个饮食组中，O3暴露后肺部和BAL中的谷胱甘肽和尿酸也增加了（40 - 570%），并且在恢复期这些水平仍保持升高。肺部α - 生育酚不受O3影响。在暴露后和恢复后，AH2缺乏的豚鼠中出现了与饮食相关的显著总体下降。总之，1周O3暴露和恢复后的肺损伤/炎症受AH2缺乏的影响最小。尽管缺乏AH2，但抗氧化剂似乎也会因O3暴露而增加。
