Defence R & D Establishment, Gwalior, India.
Toxicol Mech Methods. 2011 Oct;21(8):596-605. doi: 10.3109/15376516.2011.576713. Epub 2011 May 9.
Sulfur mustard (SM) (bis-(2-chloroethyl) sulfide) is a chemical warfare agent. Evaluation of toxicity and protective effect of DRDE-07 (S-2(2-aminoethylamino)ethyl phenyl sulfide) was studied in mouse liver after SM challenging. Female mice were given orally 0.2 LD(50) of DRDE-07 (249 mg/kg body weight) and exposed percutaneously with 1.0 LD(50) of SM (8.1 mg/kg body weight). Gene expression profiles were determined using global genome microarray analysis at 3 days post-exposure. DRDE-07 alone treated animal showed significant upregulation to metabolism of xenobiotics by cytochrome P450 pathways. Genes related to cell adhesion molecules (CAMs), were downregulated. DRDE-07 pretreated SM exposed animals showed upregulation of xenobiotic cytochrome P450 pathway genes. Antigen presenting, cell adhesion molecules, cytokine, cytokine receptor metabolism, fatty acid metabolism, glutathione metabolism, cell cycle signaling pathway genes showed downregulation. The present study showed that SM-induced toxicity in mouse liver was attenuated by the pretreatment with DRDE-07.
硫芥（SM）（双-（2-氯乙基）硫醚）是一种化学战剂。研究了在 SM 攻击后，DRDE-07（S-2（2-氨乙基氨基）乙基苯硫醚）在小鼠肝脏中的毒性评估和保护作用。雌性小鼠经口给予 0.2LD（50）的 DRDE-07（249mg/kg 体重），并经皮暴露于 1.0LD（50）的 SM（8.1mg/kg 体重）。在暴露后 3 天，使用全基因组微阵列分析来确定基因表达谱。单独用 DRDE-07 处理的动物显示细胞色素 P450 途径对外源化学物质代谢的显著上调。与细胞粘附分子（CAM）相关的基因下调。DRDE-07 预处理的 SM 暴露动物显示出对外源化学物质细胞色素 P450 途径基因的上调。抗原呈递、细胞粘附分子、细胞因子、细胞因子受体代谢、脂肪酸代谢、谷胱甘肽代谢、细胞周期信号通路基因下调。本研究表明，DRDE-07 预处理可减轻 SM 诱导的小鼠肝脏毒性。
