The mouse ear
vesicant model (MEVM) provides a quantitative
edema response as well as histopathological and biochemical endpoints as measurements of
inflammation and tissue damage following exposure to the
chemical warfare agent sulfur mustard (HD). In the MEVM, several topically applied
anti-inflammatory agents provided a significant degree of protection against HD-induced
edema and dermal-epidermal separation. This study evaluated the protective effects of three of these pharmacological compounds when administered systemically in the MEVM. Alzet osmotic pumps were used to deliver a subcutaneous dose of the appropriate
anti-inflammatory agent, starting 24 h before exposure to
sulfur mustard and continuing until 24 h post-exposure to HD. Twenty-four hours after pump implantation, 5 microl of
a 195 mM (0.16 mg)
solution 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 each mouse.
Sulfur mustard injury in the mouse ear was measured by both
edema response (fluid accumulation) and histopathological damage (
necrosis, epidermal-dermal separation). The systemic administration of
hydrocortisone,
indomethacin 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 reduction in subepidermal
blisters (71%, 52% and 57%, respectively) whereas only
hydrocortisone produced a significant reduction in contralateral epidermal
necrosis (41%). We show here that these anti-inflammatory drugs are effective when administered systemically in the MEVM.