Proteomic and Metabolomic Profiling Identify Plasma Biomarkers for Exposure to Ultra-low Levels of Carfentanil

Abstract Despite the recent epidemic of fentanyl abuse, there are few validated assays capable of rapidly detecting these compounds. In order to improve the ability to detect carfentanil at physiologically relevant concentrations, we developed a systems biology approach to discover host-based marker...

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Bibliographic Details
Published in:Toxicological sciences 2019-02, Vol.167 (2), p.524-535
Main Authors: Dhummakupt, Elizabeth S, Rizzo, Gabrielle M, Feasel, Michael, Mach, Phillip M, Tran, Bao Q, Carmany, Daniel O, Demond, Paul S, McBride, Ethan M, Maughan, Michele, Sekowski, Jennifer W, Glaros, Trevor
Format: Article
Language:English
Subjects:
Analgesics, Opioid - blood
Animals
Biomarkers - blood
Blood Proteins - analysis
Chromatography, Reverse-Phase
Environmental Exposure - analysis
Fentanyl - analogs & derivatives
Fentanyl - blood
Inhalation Exposure - analysis
Male
Mass Spectrometry
Metabolome - drug effects
Metabolomics - instrumentation
Metabolomics - methods
Proteomics - instrumentation
Proteomics - methods
Rabbits
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Summary:Abstract Despite the recent epidemic of fentanyl abuse, there are few validated assays capable of rapidly detecting these compounds. In order to improve the ability to detect carfentanil at physiologically relevant concentrations, we developed a systems biology approach to discover host-based markers which are specifically amplified upon exposure in a rabbit model. For this work, two “omics” pipelines utilizing mass spectrometry were developed and leveraged. First, a proteomics pipeline was developed to interrogate the blood plasma for protein-based biomarkers. Due to the incredible dynamic range of the plasma protein content, a multi-dimensional fractionation technique was used to partition and more accurately investigate the circulating plasma proteome. Isobaric tandem mass tags were integrated into the workflow to make quantitative assessments across all animals for an extended time course post-exposure. In addition to the proteomics efforts, blood plasma was also processed through an untargeted metabolomics pipeline. This approach allows for the identification of >800 small molecule features. By processing and analyzing data sets in parallel, we were able to identify a unique fingerprint of protein and metabolite perturbations that manifest following exposure to carfentanil.
ISSN:1096-6080
1096-0929
DOI:10.1093/toxsci/kfy259