Biochemical Markers and Synthetic Protease Inhibitors in Animal Models of Sulfur Mustard Vesication

摘要

Sulfur mustard (SM) is a potent vesicant which penetrates the skin rapidly and causes extensive blistering. SM can alkylate DNA, RNA, and proteins which results in inflammation, tissue damage, and cell death. Many of the proteases released by SM exposure attack connective tissue proteins. It is likely that proteases are responsible for the formation of the fluid filled blisters which occur after SM exposure. Tissue homogenates harvested from the ears of mice or the backs of euthymic hairless mice exposed to SM were assayed for protease activities using chromogenic and fluorogenic substrates. SM exposed skin homogenates have higher protease activities than the control samples in both animal models. Three specific protease inhibitors reduce the protease activities of the exposed and control samples in both animal models. Skin tissue homogenates pretreated with anti-inflammatory drugs, protease inhibitors, or a combination of the two prior to the SM exposure have lower protease activities than untreated samples. Protease assays are useful in measuring the extent and progress of SM induced vesication and can be used to measure the effectiveness of drug treatments. Protease inhibitors and antiinflammatory drugs alone or in combination may have therapeutic use in reducing tissue injury caused by SM exposure.