Metabonomics of Pig Blood Plasma Following Whole Body Exposure to Low Levels of Gb Vapor

摘要

Chemometric approaches have the potential to enhance defense operations against chemical warfare agents (CWAs), for which complex data must be analyzed. Therefore, we have begun an exploration of the use of chemometrics for the correlation of metabolic change with low-level CWA exposure in animal models. In this exploratory study, pigs were exposed to GB (sarin) over a range of concentrations (0.028-0.310 mg/cubic meters) and exposure times (0-180 minutes). Blood (4-8 mL) was collected periodically during miosis-level exposure and the plasma analyzed by proton nuclear magnetic resonance spectroscopy (NMR) at 500 MHz. Principle component (PC) analysis of a small preliminary data set resulted in a PC2 PC1 scores plot showing clustering of the spectra from exposed pigs. Variance highlighted by the first and second principal components corresponded to specific spectral regions which were tentatively assigned to EDTA/choline (NMR peaks overlap) and lactate. Lactate concentration was found to vary in a parallel clinical analysis. The results of this initial study indicate that a combination of chemometrics and NMR will yield metabonomics data useful for establishing biochemical markers for agent exposure. Ideally, such markers would identify metabolic changes that occur prior to visible external symptoms (e.g. miosis, convulsions).