Ghio Andrew J, Roggli Victor L, Richards Judy H, Crissman Kay M, Stonehuerner Jacqueline D, Piantadosi Claude A
National Health and Environmental Effects Research Laboratory, Environmental Protection Agency, Research Triangle Park, NC, USA.
Hum Pathol. 2003 Aug;34(8):737-42. doi: 10.1016/s0046-8177(03)00252-1.
We report on a deposition of oxalate crystals on ferruginous bodies after occupational exposure to asbestos demonstrated in 3 patients. We investigated the mechanism and possible significance of this deposition by testing the hypothesis that oxalate generated through nonenzymatic oxidation of ascorbate by asbestos-associated iron accounts for the deposition of the crystal on a ferruginous body. Crocidolite asbestos (1000 microg/mL) was incubated with 500 micromol H(2)O(2) and 500 micromol ascorbate for 24 hours at 22 degrees C. The dependence of oxalate generation on iron-catalyzed oxidant production was tested with the both the metal chelator deferoxamine and the radical scavenger dimethylthiourea. Incubation of crocidolite, H(2)O(2), and ascorbate in vitro generated approximately 42 nmol of oxalate in 24 hours. Oxalate generation was diminished significantly by the inclusion of either deferoxamine or dimethylthiourea in the reaction mixture. Incubation of asbestos bodies and uncoated fibers isolated from human lung with 500 micromol H(2)O(2) and 500 micromol ascorbate for 24 hours at 22 degrees C resulted in the generation of numerous oxalate crystals. We conclude that iron-catalyzed production of oxalate from ascorbate can account for the deposition of this crystal on ferruginous bodies.
我们报告了3例职业性接触石棉后,草酸钙晶体在含铁小体上的沉积情况。我们通过检验以下假设来研究这种沉积的机制及其可能的意义:石棉相关铁通过非酶促氧化抗坏血酸生成的草酸导致晶体在含铁小体上沉积。将青石棉(1000微克/毫升)与500微摩尔过氧化氢和500微摩尔抗坏血酸在22℃下孵育24小时。用金属螯合剂去铁胺和自由基清除剂二甲基硫脲测试草酸生成对铁催化氧化剂产生的依赖性。青石棉、过氧化氢和抗坏血酸在体外孵育24小时可产生约42纳摩尔草酸。在反应混合物中加入去铁胺或二甲基硫脲可显著减少草酸的生成。将从人肺中分离出的石棉小体和未包被纤维与500微摩尔过氧化氢和500微摩尔抗坏血酸在22℃下孵育24小时,导致大量草酸钙晶体生成。我们得出结论,铁催化抗坏血酸生成草酸可以解释这种晶体在含铁小体上的沉积。