Multiple metabolic pathways are predictive of ricin intoxication in a rat model

Research output: Contribution to journalArticle

Authors

  • Riccardo D’Elia
  • Sarah Goodchild
  • Fiona Stahl
  • Cerys Docx
  • Vikesh Patel
  • A. Christopher Green
  • Roman Lukaszewski

Colleges, School and Institutes

External organisations

  • Dstl Porton Down

Abstract

Introduction
Exposure to ricin can be lethal and treatments that are under development have short windows of opportunity for administration after exposure. It is therefore essential to achieve early detection of ricin exposure to provide the best prognosis for exposed individuals. Ricin toxin can be detected in clinical samples via several antibody-based techniques, but the efficacy of these can be limited due to the rapid processing and cellular uptake of toxin in the body and subsequent low blood ricin concentrations. Other diagnostic tools that perform, in an orthogonal manner, are therefore desirable.

Objectives
To determine time-dependent metabolic changes in Sprague–Dawley rats following intravenous exposure to ricin.

Methods
Sprague–Dawley rats were intravenously exposed to ricin and multiple blood samples were collected from each animal for up to 48 h following exposure in two independent studies. Plasma samples were analysed applying HILIC and C18 reversed phase UHPLC–MS assays followed by univariate and multivariate analysis.

Results
In Sprague–Dawley rats we have demonstrated that metabolic changes measured in blood can distinguish between rats exposed intravenously to ricin and controls prior to the onset of behavioral signs of intoxication after 24 h. A total of 37 metabolites were significantly altered following exposure to ricin when compared to controls. The arginine/proline, bile acid and triacylglyceride metabolic pathways were highlighted as being important with two triacylglycerides at 8 h post exposure giving an AUROC score of 0.94. At 16 h and 24 h the AUROC score increased to 0.98 and 1.0 with the number of metabolites in the panel increasing to 5 and 7, respectively.

Conclusions
These data demonstrate that metabolites may be a useful tool to diagnose and detect ricin exposure, thus increasing the effectiveness of supportive therapy and future ricin-specific medical treatments.

Details

Original languageEnglish
Article number102
Number of pages15
JournalMetabolomics
Volume15
Issue number7
Publication statusPublished - 3 Jul 2019

Keywords

  • Ricin, Metabolomics, Arginine/proline metabolism, Bile acid metabolism, Triacylglyceride metabolism