Phenidone and hydroxyurea reduce sulfur mustard-increased proteolysis in hairless guinea pig skin
Increased proteolytic activity at the dermal-epidermal junction is postulated as being involved in sulfur-mustard-induced cutaneous injury. Homogenates of skin punch biopsy specimens from the skin of hairless guinea pig at 6, 9, 12, and 24 h after a 7 min vapor cup exposure to sulfur mustard (HD) demonstrated enhanced proteolytic activity. Homogenates from the biopsy specimens of exposed animals produced from 3 to 10 times the hydrolysis of the chromogenic peptide substrate Chromzym TH (tosyl-gly-pro-arg-p-nitrani-lide) and human elastase substrate N-methoxysuccinyl-ala- ala-pro-val-p-nitranilide than did the homogenates from control samples. In this study HD-increased proteolysis of the TH substrate by extracts of hairless guinea pig skin biopsies was nearly eliminated by systemic treatment with hydroxyurea and greatly reduced by topical application of the anti-inflammatory compound phenidone. Compounds that reduce HD-increased proteolytic activity, such as phenidone and hydroxyurea, can serve as probes to examine the role of proteolysis in HD-induced pathology. HD-increased proteolysis provides a biochemical correlate for investigating cutaneous exposure to HD. Increased proteolysis may therefore serve as a biomarker for HD-induced pathology that might be used as an index of efficacy for potential treatment compounds.
- Research Organization:
- Army Medical Research Inst. of Chemical Defense, Aberdeen Proving Ground, MD (United States)
- OSTI ID:
- 273175
- Report Number(s):
- AD-A--306790/7/XAB; USAMRICD-P--95-003-561
- Country of Publication:
- United States
- Language:
- English
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