Use of Epidermolysis Bullosa Biomarkers in Models of Vesicant Injury
Final rept. 15 May 2002-31 Aug 2006
RUTGERS - THE STATE UNIV PISCATAWAY NJ
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This study consisted of an SM time course study for gene expression of protease and extracellular matrix related genes and an evaluation of potential medical countermeasures for SM-induced injury in the mouse ear vesicant model. The specific aim of the time course study was to determine whether MMP and MMP substrate laminin-332 gene expression levels are altered over time 6, 12, 24, 72, 168 h in mouse ear skin topically exposed to liquid SM. The specific aim of the compound evaluation study was to determine the effectiveness of topically delivered synthetic MMP inhibitors, Ilomastat, GM1489, MMP- 2MMP-9 Inhibitor I, and MMP-2MMP-9 Inhibitor II, to protect against SM injury. Protection was quantitatively assessed by measuring MMP and MMP substrate gene expression levels with subsequent correlation to histopathological damage in tissues harvested at 24 h, 72 h and 7 days after SM challenge. Pre-treatment with Ilomastat in conjunction with SM exposure significantly decreased laminin- 2 expression at 72 h and significantly increased laminin332- 3A expression at 72 h as compared to SM-only no drug compound pre-treatment. This coincided with a slightly improved Draize Score at 72 h with Ilomastat pre-treatment as compared to the other compounds. Pre-treatment with GM1489 in conjunction with SM exposure significantly decreased MMP-9 expression at 72 h and decreased MMP-2 expression at 7 days as compared to SM-only.
- Medicine and Medical Research
- Chemical, Biological and Radiological Warfare