Schapira R M, Ghio A J, Effros R M, Morrisey J, Almagro U A, Dawson C A, Hacker A D
Division of Pulmonary and Critical Care Medicine, Medical College of Wisconsin.
Am J Respir Cell Mol Biol. 1995 Feb;12(2):220-6. doi: 10.1165/ajrcmb.12.2.7865220.
The hydroxyl radical (.OH) is a highly reactive oxygen free radical that has been implicated as a cause of lung injury following exposure to silica and silicates. Despite evidence that silica generates .OH in vitro, there has been no previous demonstration of in vivo production of .OH after exposure to nonfibrous mineral oxide dusts. We tested the hypothesis that instillation of silica into rat lungs is associated with greater .OH production and acute lung inflammation in vivo relative to the instillation of a less toxic nonsilicate particle, titanium dioxide. The production of .OH in the lungs following dust instillation was measured using sodium salicylate as an .OH trap. Seven days after dust exposure, the rats were given intraperitoneal salicylate, the lungs isolated, and salicylate hydroxylation products (2,3- and 2,5-dihydroxybenzoic acid), reflecting .OH, were measured. There was significantly more 2,3-dihydroxybenzoic acid in silica-exposed lungs compared with lungs instilled with titanium dioxide. In addition, the instillation of silica into rat lungs in vivo was associated with a greater acute inflammatory response. We conclude that following in vivo exposure, silica stimulates greater .OH production relative to the less toxic particle, titanium dioxide. These differences in .OH generation correspond to disparities in acute lung inflammation.
羟基自由基（·OH）是一种活性很强的氧自由基，它被认为是接触二氧化硅和硅酸盐后导致肺损伤的原因之一。尽管有证据表明二氧化硅在体外能产生·OH，但此前尚无关于接触非纤维性矿物氧化物粉尘后体内产生·OH的报道。我们验证了这样一个假设：相对于注入毒性较小的非硅酸盐颗粒二氧化钛，向大鼠肺部注入二氧化硅会在体内产生更多的·OH并引发更严重的急性肺部炎症。通过使用水杨酸钠作为·OH捕获剂来测定粉尘注入后肺部·OH的生成量。在接触粉尘7天后，给大鼠腹腔注射水杨酸盐，然后分离肺部，并测定反映·OH的水杨酸盐羟基化产物（2,3 - 二羟基苯甲酸和2,5 - 二羟基苯甲酸）。与注入二氧化钛的肺部相比，接触二氧化硅的肺部中2,3 - 二羟基苯甲酸的含量显著更高。此外，向大鼠肺部体内注入二氧化硅与更强烈的急性炎症反应相关。我们得出结论，在体内接触后，相对于毒性较小的颗粒二氧化钛，二氧化硅会刺激产生更多的·OH。这些·OH生成量的差异与急性肺部炎症的差异相对应。
