Defence Research and Development Establishment, Gwalior, India.
Hum Exp Toxicol. 2010 Sep;29(9):747-55. doi: 10.1177/0960327109359641. Epub 2010 Feb 17.
Despite extensive research efforts, there is no unanimous approval of any animal model to evaluate the toxicity of sulphur mustard [SM; bis (2-chloroethyl) sulphide] or nitrogen mustard [HN-3; tris-(2-chloroethyl) amine] and screening of various prophylactic and therapeutic agents against them. In this study, differential toxicity of mustard agents in higher animal model that is male rabbit was determined. Protective efficacy of DRDE 07 [S-2(2-aminoethylamino) ethyl phenyl sulphide] and its analogues were also evaluated against SM and HN-3 toxicity. Differential toxicity study of SM and HN-3 reveals that both the compounds were more toxic by percutaneous route as compared to subcutaneous route. Till date, there is no recommended drug to counteract SM induced toxicity or mortality in vivo. However, DRDE 07 (an amifostine analogue) and its analogues are found to be very effective protective agents against percutaneously exposed SM in rabbits. The present experiments also showed that SM does not cause skin injury alone but also can cause systemic toxicity as well. DRDE 07 and many of its analogues may prove as prototype compounds for the development of better prophylactic and therapeutic drugs to counter the toxicity of SM or HN-3. In conclusion, rodents and rabbits can be used for the screening of drugs against the blistering agents.
尽管进行了广泛的研究工作，但对于哪种动物模型可用于评估芥子气[SM；双（2-氯乙基）硫醚]或氮芥[HN-3；三（2-氯乙基）胺]的毒性以及筛选针对它们的各种预防和治疗药物，尚无一致认可。在这项研究中，确定了雄性兔这一高等动物模型中芥子气类化合物的差异毒性。还评估了 DRDE 07[ S-2（2-氨乙基氨基）乙基苯硫醚]及其类似物对 SM 和 HN-3 毒性的防护效果。SM 和 HN-3 的差异毒性研究表明，与皮下途径相比，这两种化合物经皮途径的毒性更大。迄今为止，尚无推荐的药物可对抗体内 SM 引起的毒性或死亡率。然而，DRDE 07（一种氨磷汀类似物）及其类似物被发现是对抗兔经皮暴露 SM 的非常有效的保护剂。目前的实验还表明，SM 不仅会单独引起皮肤损伤，还会引起全身毒性。DRDE 07 和许多类似物可能被证明是开发更好的预防和治疗药物以对抗 SM 或 HN-3 毒性的原型化合物。总之，啮齿动物和兔可用于筛选针对水疱形成剂的药物。
