Protective effect of topical iodine containing anti-inflammatory drugs against sulfur mustard-induced skin lesions

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• 作者：Uri Wormser (1) (2) (3)
  Amnon Sintov (4)
  Berta Brodsky (3)
  Robert P. Casillas (5)
  Abraham Nyska (6)
  
• 关键词：Sulfur mustard ; Mustard gas ; Skin toxicity ; Dermatotoxicity ; Iodine ; Anti ; inflammatory agents
• 刊名：Archives of Toxicology
• 出版年：2004
• 出版时间：March 2004
• 年：2004
• 卷：78
• 期：3
• 页码：156-166
• 全文大小：2119KB
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• 作者单位：Uri Wormser (1) (2) (3)
  Amnon Sintov (4)
  Berta Brodsky (3)
  Robert P. Casillas (5)
  Abraham Nyska (6)
  
  1. Berman Building, Institute of Life Sciences, The Hebrew University, 91904, Jerusalem, Israel
  2. David R. Bloom Center for Pharmacy, The Hebrew University, Jerusalem, Israel
  3. Department of Pharmacology, School of Pharmacy, Faculty of Medicine, The Hebrew University, 91172, Jerusalem, Israel
  4. Institutes for Applied Research, Ben Gurion University of the Negev, 84105, Beer-Sheva, Israel
  5. Medical Research and Evaluation Facility, Battelle, Columbus, OH, 43201-693, USA
  6. Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27713, USA
  
• ISSN：1432-0738

文摘

Previous studies have shown the antidotal efficacy of topical iodine at 15 and 30?min post-exposure to sulfur mustard (SM). Here we demonstrate efficacy at longer intervals (20, 30, 45, and 60?min, respectively, for data) using an improved topical povidone-iodine preparation termed N66, which contains steroidal and non-steroidal anti-inflammatory agents. In the mouse, N66 reduced severity of ear edema by 43, 47, 44, and 36%; ear epidermal ulceration by 74, 58, 45, and 58%; and epidermal necrosis by 54, 34, 26, and 31% at the respective time points. A similar effect was observed with encrustation. The healing marker, grade of acanthotic area, showed dramatic increases of 39.6-, 25.3-, 20.9-, and 22-fold. Severity of the dermal parameters, acute inflammation and dermal necrosis, was reduced by 63, 34, 34, and 38% and 80, 54, 54, and 59%, respectively. In guinea pig skin, topical treatment with N66 45?min post-exposure reduced the SM-induced ulceration area by 75%. The histological parameters subepidermal microblister formation, epidermal ulceration, epidermal necrosis, and encrustation were reduced by 63, 61, 41, and 41%, respectively. The healing marker, grade of acanthotic area, was elevated by 73%. N66 induced a statistically significant reduction in two dermal markers for tissue damage: acute inflammation (33%) and dermal necrosis (48%). Reduced skin damage was also observed in areas adjacent the treated sites. The pharmacologically active components of N66 showed additive effect. These findings suggest that the povidone-iodine preparation combined with anti-inflammatory agents functions as a potent antidote against skin lesions induced by SM at relatively long intervals between exposure and treatment.