Transition and Use of the Mouse Ear Model for Evaluating Candidate Pre- and Post-Treatrnents for Efficacy Against Percutaneous Sulfur Mustard Exposure at the Medical Research and Evaluation Facility

摘要

The mouse ear model has been used at the U.S. Army Medical Institute of chemical Defense (USAMRICD) to assess dermal injury caused by sulfur mustard (HD) and to evaluate potential pre- and posttreatment compounds for efficacy against percutaneous HD injury. In this model, the effects of HD with or without treatment compounds are evaluated macroscopically by edema and microscopically by histopathological changes associated with HD injury. The objectives of Task 9543 were first to transition this technique to the Battelle Medical Research and Evaluation Facility (MREF), and then to evaluate candidate antivesicant drugs for their efficacy at eliminating or lessening the effects of HD-induced tissue damage. The MREF has evaluated 334 candidate HD treatment compounds provided by USAMRICD, and 73 passed the initial screening. Of these, 23 were anti-inflammatory agents, 21 were protease inhibitors, 15 were inhibitors of poly-ADP-ribose polymerase, 12 were HD scavengers, and 2 were other classes of compounds. Several of the successful HD scavengers and anti-inflammatory agents were also tested as posttreatments (applied 10 minutes after HD) and showed some efficacy.