Systemic administration of candidate antivesicants to protect against topically applied sulfur mustard in the mouse ear vesicant model (MEVM)

The mouse ear vesicant model (MEVM) provides a quantitative edema response as well as histopathological and biochemical endpoints as measurements of i nflammation and tissue damage following exposure to the chemical warfare ag ent sulfur mustard (HD), In the MEVM, several topically applied anti-inflam matory agents provided a significant degree of protection against HD-induce d edema and dermal-epidermal separation. This study evaluated the protectiv e effects of three of these pharmacological compounds when administered sys temically in the MEVM. Alzet osmotic pumps were used to deliver a subcutane ous dose of the appropriate anti-inflammatory agent, starting 24 h before e xposure to sulfur mustard and continuing until 24 h post-exposure to HD, Tw enty-four hours after pump implantation, 5 mul of a 195 mM (0.16 mg) soluti on of sulfur mustard (density = 1.27 g ml(-1); MW = 159; purity = 97.5%) in methylene chloride was applied to the inner surface of the right ear of ea ch mouse. Sulfur mustard injury in the mouse ear was measured by both edema response (fluid accumulation) and histopathotogical damage (necrosis, epid ermal-dermal separation). The systemic administration of hydrocortisone, in domethacin and olvanil provided a significant reduction in edema (24%, 26% and 22%, respectively) from the positive control. Compared to HD-positive c ontrols, hydrocortisone, indomethacin and olvanil caused a significant redu ction in subepidermal blisters (71%, 52% and 57%, respectively) whereas onl y hydrocortisone produced a significant reduction in contralateral epiderma l necrosis (41%), We show here that these anti-inflammatory drugs are effec tive when administered systemically in the MEVM. Published in 2000 by John Wiley & Sons, Ltd.