Protective effect of topical iodine containing anti-inflammatory drugs against sulfur mustard-induced skin lesions.
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.
Wormser
Uri
U
Berman Building, Institute of Life Sciences, The Hebrew University, 91904 Jerusalem, Israel. wormser@cc.huji.ac.il
Sintov
Amnon
A
Brodsky
Berta
B
Casillas
Robert P
RP
Nyska
Abraham
A
D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002619:Chemical Warfare Agents / Q000633:toxicity*; D002990:Clobetasol / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004338:Drug Combinations; D004427:Ear Diseases / Q000517:prevention & control; D004487:Edema / Q000517:prevention & control; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009151:Mustard Gas / Q000633:toxicity*; D010894:Piroxicam / Q000627:therapeutic use*; D011206:Povidone-Iodine / Q000008:administration & dosage / Q000627:therapeutic use*; D020011:Protective Agents / Q000627:therapeutic use*; D012867:Skin / Q000187:drug effects* / Q000473:pathology; D012871:Skin Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D023422:Skin Irritancy Tests; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D002619:Chemical Warfare Agents; D004338:Drug Combinations; D020011:Protective Agents; D010894:Piroxicam; D011206:Povidone-Iodine; D002990:Clobetasol; D009151:Mustard Gas