Gupta Alka, Vijayaraghavan Rajagopalan, Gautam Anshoo
Department of Pharmacy, Sarojini Naidu Medical College, Mantola, Agra, 282002, India.
Department of Research and Development, Saveetha Institute of Medical and Technical Sciences, Thandalam, Chennai, 602105, India.
Toxicol Rep. 2021 Mar 17;8:599-606. doi: 10.1016/j.toxrep.2021.03.011. eCollection 2021.
Sulfur mustard (SM) is chemically, bis(2-chloroethyl) sulfide and a strong alkylating agent that causes cytotoxicity and blisters on skin. In laboratory animal models, SM is extremely lethal. Since no specific antidote has been proposed, decontamination upon contact is the recommended procedure. Several antidotes have been screened for SM, and in that sulfanyl compounds, N-acetyl-l-cysteine (NAC) and S-2(2-aminoethylamino) ethylphenyl sulfide (DRDE-07) showed good protection. Since they showed protection at high doses, the aim of this study was to evaluate the efficacy in combination at low dose, for percutaneously administered SM in mice.
4 LD of SM (32.4 mg/kg) was administered, and NAC (50 mg/kg), DRDE-07 (25 and 50 mg/kg) and their combinations were evaluated as 30 min pre-treatment by single oral administration.
After 72 h of SM exposure, significant decrease in body weight, decrease in hepatic reduced glutathione, and increase in hepatic malondialdehyde were observed (P < 0.001), showing oxidative stress. The combination of NAC (100 mg/kg) and DRDE-07 (50 mg/kg) showed significant protection (P < 0.01). The severe histopathological lesions induced by SM in liver, spleen and skin were also considerably reduced by the combination.
The combination of NAC and DRDE-07 having sulfanyl groups, will be promising antioxidants and an effective antidote for SM toxicity.
硫芥（SM）化学名称为双（2-氯乙基）硫醚，是一种强烷基化剂，可导致细胞毒性并使皮肤起水疱。在实验动物模型中，硫芥具有极高的致死性。由于尚未提出特异性解毒剂，接触后进行去污处理是推荐的程序。已经筛选了几种针对硫芥的解毒剂，其中硫醇化合物N-乙酰-L-半胱氨酸（NAC）和S-2（2-氨基乙氨基）乙苯硫醚（DRDE-07）显示出良好的保护作用。由于它们在高剂量时显示出保护作用，本研究的目的是评估低剂量联合使用时对经皮给予硫芥的小鼠的疗效。
给予4倍半数致死量的硫芥（32.4 mg/kg），并将NAC（50 mg/kg）、DRDE-07（25和50 mg/kg）及其组合作为单次口服预处理30分钟进行评估。
硫芥暴露72小时后，观察到体重显著下降、肝脏还原型谷胱甘肽减少以及肝脏丙二醛增加（P < 0.001），表明存在氧化应激。NAC（100 mg/kg）和DRDE-07（50 mg/kg）的组合显示出显著的保护作用（P < 0.01）。硫芥在肝脏、脾脏和皮肤中诱导的严重组织病理学损伤也因该组合而显著减轻。
具有硫醇基团的NAC和DRDE-07组合有望成为抗氧化剂以及治疗硫芥中毒的有效解毒剂。
