Long-term exposure to ozone increases acute pulmonary centriacinar injury by 1-nitronaphthalene: II. Quantitative histopathology.
Long-term exposure to ozone increases acute pulmonary centriacinar injury by 1-nitronaphthalene: II. Quantitative histopathology.
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发表时间：
2000-12
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通讯作者：
R. Paige;V. Wong;C. Plopper
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作者：
R. Paige;V. Wong;C. Plopper
长期接触氧化性空气污染物臭氧(O(3))与对氧化剂损伤的急性影响的耐受性有关。为了测试这种对急性损伤的抵抗力是否延伸到生物活性肺部毒物，雄性SD大鼠暴露于过滤空气(FA)或0.8ppm O(3)(8h/d)中90天，并给予1-硝基-萘。剂量分别为0、50或100毫克/公斤。1-硝基萘是一种需要代谢活化的肺部细胞毒物。高分辨率组织病理学、透射电子显微镜和形态计量学显示，与FA暴露的大鼠相比，O(3)-的中央腺泡区域的1-硝基-萘毒性显著增加。在100 mg/kg剂量下，O(3)染毒大鼠末梢细支气管壁86%的基底膜被剥离，78%的上皮细胞坏死。相比之下，服用100 mg/kg 1-硝基萘的FA暴露大鼠，4%的基底膜被剥离；仅有25%的上皮细胞坏死。用1-硝基萘处理的FA和O(3)暴露大鼠之间的关键区别在于O(3)暴露动物纤毛细胞毒性的严重程度。尽管长期暴露在臭氧中会产生中央腺泡上皮对氧化应激的耐受性，但这是事实。在过滤空气和臭氧暴露的大鼠之间，肺内呼吸道或气管对1-硝基萘的敏感性没有差异。这项研究表明，在急性肺损伤的产生过程中，臭氧和1-硝基-萘之间存在着位置选择性的协同作用。
Long-term exposure to the oxidant air pollutant ozone (O(3)) is associated with tolerance to the acute effects of oxidant injury. To test whether this resistance to acute injury extends to bioactivated pulmonary toxicants, male Sprague-Dawley rats were exposed to filtered air (FA) or 0.8 ppm O(3) (8 h/day) for 90 days and administered 1-nitronaphthalene i.p. at doses of 0, 50, or 100 mg/kg. 1-Nitronaphthalene is a pulmonary cytotoxicant requiring metabolic activation. High-resolution histopathology, transmission electron microscopy, and morphometry revealed significantly greater 1-nitronaphthalene toxicity in the central acinar region of O(3)- compared with FA-exposed rats. At 100 mg/kg, injury to terminal bronchioles in O(3)-exposed rats involved denudation of 86% of the basement membrane; 78% of the cells remaining on the epithelium were necrotic. This is compared with denudation of 4% of the basement membrane of FA-exposed rats administered 100 mg/kg 1-nitronaphthalene; only 25% of the cells remaining on the epithelium were necrotic. The key difference between FA- and O(3)-exposed rats treated with 1-nitronaphthalene was the heightened severity of ciliated cell toxicity in O(3)-exposed animals. This is despite the fact that long-term exposure to ozone produces tolerance to oxidant stress in the epithelium of the central acinus. No differences in the susceptibility of intrapulmonary airways or trachea to 1-nitronaphthalene were observed between filtered air- and ozone-exposed rats. This study demonstrates a site-selective synergy between the copollutants ozone and 1-nitronaphthalene in the production of acute lung injury.