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 incapacitation. Although there has been long and intensive efforts to find a treatment 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 topical 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 many studies, including vesicants. Neat HD, either in liquid form (0.2-1 microl droplets) or as vapour, was applied to the back skin of female pigs (a cross Large White & Landrace, 10-12 kg) for various exposure durations. Evaluation was based on quantitative analysis of the degree of erythema and area of the lesions, as well as histological 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 ointments 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 containing lidocaine or pentamide produce beneficial effects when applied immediately after short-term HD exposure to pig skin.
Kadar
T
T
Israel Institute for Biological Research, Ness Ziona.
Fishbeine
E
E
Meshulam
Y
Y
Sahar
R
R
Chapman
S
S
Liani
H
H
Barness
I
I
Amir
A
A
D000287:Administration, Topical; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001768:Blister / Q000139:chemically induced* / Q000188:drug therapy; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D003879:Dermatologic Agents / Q000009:adverse effects*; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007271:Injections, Intradermal; D008012:Lidocaine / Q000008:administration & dosage / Q000494:pharmacology; D009151:Mustard Gas / Q000009:adverse effects*; D011343:Procaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D013552:Swine; D013881:Thioridazine / Q000008:administration & dosage / Q000494:pharmacology*; D014268:Trifluoperazine / Q000008:administration & dosage / Q000494:pharmacology*
D000779:Anesthetics, Local; D002147:Calmodulin; D003879:Dermatologic Agents; D018492:Dopamine Antagonists; D014268:Trifluoperazine; D011343:Procaine; D008012:Lidocaine; C005298:benoxinate; D013881:Thioridazine; D009151:Mustard Gas