Gautam Anshoo, Gupta Alka, Lomash Vinay, Pant S C, Vijayaraghavan R
Defence Research and Development Establishment, Gwalior 474 002, India.
Indian J Exp Biol. 2010 Jul;48(7):752-61.
Sulphur mustard, [bis (2-chloroethyl)] sulphide (SM), is a bifunctional alkylating agent. SM forms sulphonium ion in the body which alkylates DNA and several other macromolecules, and induces oxidative stress. Although several antidotes have been screened for the treatment of systemic toxicity of SM in experimental animals none of them are recommended so far. In the search for more effective and less toxic antidotes, various combinations were tried against SM induced toxicity and skin lesions. SM exposed through percutaneous route was used to evaluate the prophylactic efficacy of various combinations. Low dose of DRDE-07 (S-2(2-aminoethylamino) ethyl phenyl sulphide), DRDE-30 [S-2(2-aminoethyl amino) ethyl propyl sulphide], DRDE-35 [S-2(2-aminoethyl amino) ethyl butyl sulphide] with amifostine combinations, were given orally 30 min prior to SM exposure. Significant depletion was observed in body weight, organ body weight index and hepatic GSH and GSSG content in mice after SM exposure. Pretreatment with low dose of different combinations of DRDE-07, DRDE-30 and DRDE-35 with amifostine could recover biochemical alterations and histopathological changes caused by SM exposures.
硫芥，即双（2-氯乙基）硫化物（SM），是一种双功能烷基化剂。SM在体内形成锍离子，该离子使DNA和其他几种大分子发生烷基化，并诱导氧化应激。尽管已经在实验动物中筛选了几种用于治疗SM全身毒性的解毒剂，但到目前为止，尚未推荐使用任何一种。为了寻找更有效且毒性更小的解毒剂，人们尝试了各种组合来对抗SM诱导的毒性和皮肤损伤。通过经皮途径接触SM来评估各种组合的预防效果。在接触SM前30分钟口服低剂量的DRDE-07（S-2（2-氨基乙氨基）乙苯硫醚）、DRDE-30 [S-2（2-氨基乙氨基）乙丙硫醚]、DRDE-35 [S-2（2-氨基乙氨基）乙丁硫醚]与氨磷汀的组合。接触SM后，小鼠的体重、器官体重指数以及肝脏谷胱甘肽（GSH）和氧化型谷胱甘肽（GSSG）含量均出现显著下降。用低剂量的DRDE-07、DRDE-30和DRDE-35与氨磷汀的不同组合进行预处理，可以恢复由接触SM引起的生化改变和组织病理学变化。
