Systemic administration of candidate antivesicants to protect against topically applied suitor 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 IID, T wenty-four hours after pump implantation, 5 mul of a 195 mM (0.16 mg) solut ion of sulfur mustard (density = 1.27 g ml(-1); MW = 159; purity = 97.5%) i n methylene chloride was applied to the inner surface of the right ear of e ach mouse, Sulfur mustard injury in the mouse ear was measured by both edem a response (fluid accumulation) and histopathological damage (necrosis, epi dermal-dermal separation). The systemic administration of hydrocortisone, i ndomethacin and olvanil provided a significant reduction in edema (24%, 26% and 22%, respectively) from the positive control. Compared to HD-positive controls, hydrocortisone, indomethacin and olvanil caused a significant red uction in subepidermal blisters (71%, 52% and 57%, respectively) whereas on ly hydrocortisone produced a significant reduction in contralateral epiderm al necrosis (41%), We show here that these anti-inflammatory drugs are effe ctive when administered systemically in the MEVM.