Pino Maria A, Billack Blase
Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St. John's University, Jamaica, New York, USA.
Cutan Ocul Toxicol. 2008;27(3):161-72. doi: 10.1080/15569520802092070.
Mechlorethamine (HN2) and 2-chloroethylethyl sulfide (CEES) are mustard vesicants. Butylated hydroxyanisole (BHA) is a phenolic antioxidant. In the present work, the ability of BHA to reduce the toxicity of HN2 and CEES was investigated using A-431 skin cells. HN2 toxicity was found to be dependent, at least in part, on the cellular glutathione (GSH) status. BHA also decreased HN2-induced DNA damage and lipid peroxidation. The cytoprotective activity of BHA was also compared with that of the structurally unrelated antioxidant ebselen. Whereas ebselen (30 microM) protected skin cells from the toxicity of both HN2 (10-80 microM) and CEES (10-40 microM), BHA (100 microM) reduced the toxicity of HN2 only. Taken together, these data suggest that antioxidants such as BHA or ebselen may serve as useful treatments for injury caused by blistering agents.
氮芥（HN2）和2-氯乙基乙基硫醚（CEES）是芥子气糜烂剂。丁基羟基茴香醚（BHA）是一种酚类抗氧化剂。在本研究中，使用A-431皮肤细胞研究了BHA降低HN2和CEES毒性的能力。发现HN2的毒性至少部分取决于细胞内谷胱甘肽（GSH）的状态。BHA还减少了HN2诱导的DNA损伤和脂质过氧化。还将BHA的细胞保护活性与结构不相关的抗氧化剂依布硒仑进行了比较。虽然依布硒仑（30微摩尔）可保护皮肤细胞免受HN2（10 - 80微摩尔）和CEES（10 - 40微摩尔）的毒性，但BHA（100微摩尔）仅降低了HN2的毒性。综上所述，这些数据表明，BHA或依布硒仑等抗氧化剂可能是治疗起泡剂所致损伤的有效方法。
