Paromov Victor, Kumari Sudha, Brannon Marianne, Kanaparthy Naga S, Yang Hongsong, Smith Milton G, Stone William L
Department of Pharmacology, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
J Toxicol. 2011;2011:109516. doi: 10.1155/2011/109516. Epub 2011 May 30.
Sulfur mustard or mustard gas (HD) and its monofunctional analog, 2-chloroethyl ethyl sulfide (CEES), or "half-mustard gas," are alkylating agents that induce DNA damage, oxidative stress, and inflammation. HD/CEES are rapidly absorbed in the skin causing extensive injury. We hypothesize that antioxidant liposomes that deliver both water-soluble and lipid-soluble antioxidants protect skin cells from immediate CEES-induced damage via attenuating oxidative stress. Liposomes containing water-soluble antioxidants and/or lipid-soluble antioxidants were evaluated using in vitro model systems. Initially, we found that liposomes containing encapsulated glutathione (GSH-liposomes) increased cell viability and attenuated production of reactive oxygen species (ROS) in HaCaT cells exposed to CEES. Next, GSH-liposomes were tested in a human epidermal model, EpiDerm. In the EpiDerm, GSH-liposomes administered simultaneously or 1 hour after CEES exposure (2.5 mM) increased cell viability, inhibited CEES-induced loss of ATP and attenuated changes in cellular morphology, but did not reduce caspase-3 activity. These findings paralleled the previously described in vivo protective effect of antioxidant liposomes in the rat lung and established the effectiveness of GSH-liposomes in a human epidermal model. This study provides a rationale for use of antioxidant liposomes against HD toxicity in the skin considering further verification in animal models exposed to HD.
硫芥气或芥子气（HD）及其单官能类似物2-氯乙基乙基硫醚（CEES），即“半芥子气”，是能导致DNA损伤、氧化应激和炎症的烷基化剂。HD/CEES可迅速被皮肤吸收，造成广泛损伤。我们推测，递送水溶性和脂溶性抗氧化剂的抗氧化脂质体可通过减轻氧化应激保护皮肤细胞免受CEES即刻诱导的损伤。使用体外模型系统对含有水溶性抗氧化剂和/或脂溶性抗氧化剂的脂质体进行了评估。最初，我们发现含有包封型谷胱甘肽的脂质体（GSH脂质体）可提高暴露于CEES的HaCaT细胞的活力，并减少活性氧（ROS）的产生。接下来，在人表皮模型EpiDerm中对GSH脂质体进行了测试。在EpiDerm中，在CEES暴露（2.5 mM）的同时或1小时后给予GSH脂质体，可提高细胞活力，抑制CEES诱导的ATP损失，并减轻细胞形态变化，但并未降低caspase-3活性。这些发现与先前描述的抗氧化脂质体在大鼠肺中的体内保护作用相似，并证实了GSH脂质体在人表皮模型中的有效性。考虑到在暴露于HD的动物模型中进行进一步验证，本研究为使用抗氧化脂质体对抗皮肤中的HD毒性提供了理论依据。
