Inhibition of sulfur mustard-increased protease activity by niacinamide, N-acetyl-L-cysteine or dexamethasone
The pathologic mechanism of sulfur mustard-induced skin vesication is as yet undefined. Papirmeister et al. have postulated a biochemical mechanism for sulfur mustard-induced cutaneous injury involving sequelae of DNA alkylation, metabolic disruption resulting in NAD+ depletion and activation of protease. The authors have utilized a chromogenic peptide substrate assay to establish that human peripheral blood lymphocytes exposed 24 hr previously to sulfur mustard exhibited an increase in proteolytic activity. Doses of compounds known to alter the biochemical events associated with sulfur mustard exposure or reduce protease activity were tested in this system for their ability to block the sulfur mustard-induced protease activity. Treatment with niacinamide 1 hr after or with N-acetyl-L-cysteine or dexamethasone 24 hr prior to sulfur mustard exposure resulted in a decrease of 39%, 33% and 42% respectively of sulfur mustard-increased protease activity. These data suggest that therapeutic intervention into the biochemical pathways that culminate in protease activation might serve as an approach to treatment of sulfur mustard-induced pathology.
- OSTI ID:
- 5372037
- Report Number(s):
- CONF-9104107-; CODEN: FAJOE
- Journal Information:
- FASEB Journal (Federation of American Societies for Experimental Biology); (United States), Vol. 5:4; Conference: 75. annual meeting of the Federation of American Societies for Experimental Biology (FASEB), Atlanta, GA (United States), 21-25 Apr 1991; ISSN 0892-6638
- Country of Publication:
- United States
- Language:
- English
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45 MILITARY TECHNOLOGY, WEAPONRY, AND NATIONAL DEFENSE
AMIDES
BIOLOGICAL EFFECTS
CHEMICAL WARFARE AGENTS
TOXICITY
CYSTEINE
DEXAMETHASONE
PEPTIDE HYDROLASES
ENZYME ACTIVITY
BIOLOGICAL PATHWAYS
INHIBITION
METABOLISM
PATHOLOGICAL CHANGES
SKIN
ADRENAL HORMONES
AMINO ACIDS
BODY
CARBOXYLIC ACIDS
CORTICOSTEROIDS
ENZYMES
GLUCOCORTICOIDS
HORMONES
HYDROLASES
HYDROXY COMPOUNDS
KETONES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PREGNANES
PROTEINS
STEROID HORMONES
STEROIDS
THIOLS
WEAPONS
560300* - Chemicals Metabolism & Toxicology
450600 - Military Technology
Weaponry
& National Defense- Chemical & Biological- (1990)