A Medical Research and Evaluation Facility (MREF) and Studies Supporting the Medical Chemical Defense Program. Evaluation of Biomarkers for Sulfur Mustard Exposure in the Euthymic Hairless Mouse Model
Abstract
The objective of this study was to investigate the pharmacologic modulation of biomarkers for evaluating therapeutics against HD. The molecular biomarkers investigated, using a ribonuclease protection assay (RPA) to determine messenger ribonucleic acid (mRNA) levels, were mediators of inflammation, including several cytokines and chemokines, tenascin, and ornithine decarboxylase. Biochemical biomarkers investigated were serum amyloid P (SAP), interleukin-6 (IL-6), and interleukin-1 alpha (IL-1alpha) using ELISAs, and activity of myeloperoxidase (MPX) using a spectrophotometric method. Other endpoints included histopathology and edema measurements. Exposure to HE) resulted in a time-dependent increase in mRNA levels of monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-2 (MiP-2), macrophage inflammatory protein-1 alpha (MIP-1alpha) and interleukin- 1 beta (IL-1Beta). Exposure to HD also resulted in edema and apparent increases in the protein levels of SAP and IL-6, and in the activity of MPX. Four drug treatments, olvanil, dexamethasone, hydrocortisone, and indometbacin, were shown to modulate HD-induced inflammation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2000
- Accession Number
- ADA384357
Entities
People
- Carl T. Olson
- Carol L. Sabourin
- James A. Blank
- Kristi L. Buxton
- Michele M. Danne
Organizations
- Battelle Memorial Institute