Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia 24061, USA.
Int J Toxicol. 2009 Sep-Oct;28(5):425-35. doi: 10.1177/1091581809340331. Epub 2009 Aug 3.
Cyclotrimethylenetrinitramine (RDX) has been used extensively as an explosive in military munitions. Mechanisms for seizure production, seen in past animal studies, have not been described. Increased calcium levels contribute to excitotoxicity, so in this study neuroblastoma cells are loaded with calcium-indicating dye before application of 1.5 microM to 7.5 mM RDX, with fluorescence recorded for 30 cycles of 11 seconds each. The lowest concentration of RDX increases calcium fluorescence significantly above baseline for cycles 2 to 8; millimolar concentrations increase calcium fluorescence significantly above baseline for cycles 2 to 30. Increases in calcium, like those of 200 nM carbachol, are prevented with 10 mM of calcium chelator ethylene glycol-bis(beta-aminoethyl ether)-N,N,N,N tetra-acetic acid (EGTA, tetrasodium salt). Calcium channel blocker verapamil (20 microM), Ca(2+)-ATPase inhibitor thapsigargin (5 microM), and general membrane stabilizer lidocaine (10 mM) partially attenuate carbachol- and RDX-induced increases in calcium, suggesting that RDX transiently increases intracellular calcium by multiple mechanisms.
环三亚甲基三硝胺（RDX）广泛用作军用弹药中的爆炸物。过去的动物研究中观察到癫痫发作的产生机制尚未描述。钙水平的增加会导致兴奋毒性，因此在这项研究中，神经母细胞瘤细胞在用 1.5 微摩尔至 7.5 毫摩尔 RDX 处理之前用钙指示染料加载，记录 30 个 11 秒的循环的荧光。最低浓度的 RDX 使钙荧光在第 2 至 8 个循环中显著高于基线；毫摩尔浓度使钙荧光在第 2 至 30 个循环中显著高于基线。钙的增加，如 200 纳米 carbachol 引起的增加，可以通过 10 毫摩尔钙螯合剂乙二醇双（β-氨基乙基醚）-N，N，N，N-四乙酸（EGTA，四钠盐）来预防。钙通道阻滞剂维拉帕米（20 微摩尔）、钙（2+）-ATP 酶抑制剂 thapsigargin（5 微摩尔）和一般膜稳定剂利多卡因（10 毫摩尔）部分减轻了 carbachol 和 RDX 诱导的钙增加，表明 RDX 通过多种机制短暂增加细胞内钙。
