Treatment of skin injuries induced by sulfur mustard with calmodulin antagonists, using the pig model

Sulfur mustard (HD) is a potent cutaneous vesicant that penetrates rapidly through the skin, causing prolonged injuries and leading to severe incapaci tation. Although there has been long and intensive efforts to find a treatm ent for HD skin lesions, no effective treatment is available for HD-induced skin injuries, Recently, ointments containing calmodulin antagonists were found to be effective in preventing skin injuries induced by HD in hairless mice. The present study was designed to investigate the beneficial effects of top ical treatments with calmodulin antagonists against HD skin lesions in the pig model. The pig is used as a preferred animal model for human skin in ma ny studies, including vesicants. Neat HD, either in liquid form (0.2-1 mul droplets) or as vapour, was appli ed to the back skin of female pigs (a cross Large White & Landrace, 10-12 k g) for various exposure durations, Evaluation was based on quantitative ana lysis of the degree of erythema and area of the lesions, as well as histolo gical evaluation. Calmodulin antagonists (10% pentamide, 1% trifluoperazine , 2% thioridazine) and anaesthetics (20% lidocaine and 3% benoxinate) were dissolved in pluronic F-127 base according to Kim et al. (Eur. J. Pharmacol , 1996; 313: 107-114) or in saline, and were applied either topically as oi ntments or by intradermal injection, as early as 5 min post-exposure (twice a day for at least 3 days). The results demonstrated that topically applied pluronic base ointments con taining lidocaine or pentamide produce beneficial effects when applied imme diately after short-term HD exposure to pig skin. Copyright (C) 2000 John W iley & Sons, Ltd.