Bassett D J, Elbon C L, Reichenbaugh S S, Boswell G A, Stevens T M, McGowan M C, Kerr J S
Johns Hopkins University, Baltimore, Maryland 21205.
Toxicol Appl Pharmacol. 1989 Aug;100(1):32-40. doi: 10.1016/0041-008x(89)90089-6.
The phenylurea compound EDU (N-[2-(2-oxo-1-imidazolindinyl)ethyl]-N'-phenylurea) has been shown to protect plants from the damaging effects of ozone exposure. Models of rat lung injury, based on acute exposure to 2 ppm ozone for 3 hr and on exposure to 0.85 ppm ozone for 2 days, were used to determine whether EDU pretreatment of rats protected lungs from oxidant injury. Rats were pretreated with 100 mg/kg body wt EDU by ip administration for 2 days prior to and on the days of ozone exposure. No adverse toxicological effects of EDU pretreatment were observed. Lung superoxide dismutase (SOD) and catalase (CAT) activities were significantly enhanced from 636 to 882 U/lung and from 599 to 856 U/lung, respectively. One day following acute exposure (2 ppm for 3 hr), an ozone-induced increase of polymorphonuclear leukocytes (PMNs) from 0.01 to 1.18 million cells/lung was decreased to 0.68 million by EDU pretreatment. No alteration occurred in the degree of lung permeability indicated by increased lavage fluid albumin. EDU pretreatment also significantly decreased ozone-induced increases in PMN recovery after 2 days exposure to 0.85 ppm ozone from 5.54 to 2.12 million cells/lung. However, in this second case, EDU pretreatment reduced the observed ozone damage, indicated by a decrease in lavage fluid albumin and by a decrease in the macrophage and lymphocyte infiltration associated with this length of ozone exposure. The observation that EDU-treated cultured pulmonary arterial endothelial cells increased SOD and CAT activities identified a potential lung site of EDU interaction. These data demonstrated that although EDU pretreatment appears not to prevent initial ozone damage, it does reduce the infiltration of PMNs and might therefore prevent amplification of the injury associated with this cell type.
苯基脲化合物EDU（N-[2-(2-氧代-1-咪唑啉啶基)乙基]-N'-苯基脲）已被证明能保护植物免受臭氧暴露的破坏作用。基于急性暴露于2 ppm臭氧3小时和暴露于0.85 ppm臭氧2天建立的大鼠肺损伤模型，用于确定大鼠经EDU预处理是否能保护肺部免受氧化损伤。在臭氧暴露前2天及暴露当天，通过腹腔注射给予大鼠100 mg/kg体重的EDU进行预处理。未观察到EDU预处理有不良毒理学效应。肺超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性分别从636 U/肺显著提高到882 U/肺和从599 U/肺提高到856 U/肺。急性暴露（2 ppm，3小时）后一天，臭氧诱导的多形核白细胞（PMN）从0.01百万个细胞/肺增加到118万个细胞/肺，经EDU预处理后降至68万个细胞/肺。灌洗液白蛋白增加所表明的肺通透性程度未发生改变。EDU预处理还显著降低了暴露于0.85 ppm臭氧2天后臭氧诱导的PMN恢复增加，从554万个细胞/肺降至212万个细胞/肺。然而，在第二种情况下，EDU预处理减轻了观察到的臭氧损伤，表现为灌洗液白蛋白减少以及与这种臭氧暴露时长相关的巨噬细胞和淋巴细胞浸润减少。经EDU处理的培养肺动脉内皮细胞SOD和CAT活性增加的观察结果确定了EDU相互作用的潜在肺部位。这些数据表明，虽然EDU预处理似乎不能预防初始的臭氧损伤，但它确实减少了PMN的浸润，因此可能预防与这种细胞类型相关的损伤放大。
