Proteomic and Metabolomic Profiling Identify Plasma Biomarkers for Exposure to Ultra-low Levels of Carfentanil.
Toxicol Sci
; 167(2): 524-535, 2019 02 01.
Article
in En
| MEDLINE
| ID: mdl-30321427
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.
Full text:
1
Database:
MEDLINE
Main subject:
Fentanyl
/
Inhalation Exposure
/
Proteomics
/
Environmental Exposure
/
Metabolomics
/
Analgesics, Opioid
Limits:
Animals
Language:
En
Journal:
Toxicol Sci
Journal subject:
TOXICOLOGIA
Year:
2019
Type:
Article
Affiliation country:
United States