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

Area of Science:

• Toxicology
• Metabolomics
• Biomarker Discovery

Background:

• Ricin exposure is lethal, necessitating early detection for effective treatment.
• Current antibody-based ricin detection methods have limitations due to rapid toxin uptake and low blood concentrations.
• Orthogonal diagnostic tools are needed for timely ricin exposure diagnosis.

Purpose of the Study:

• To investigate time-dependent metabolic alterations in Sprague-Dawley rats after intravenous ricin exposure.
• To identify potential blood-based biomarkers for early ricin exposure detection.

Main Methods:

• Intravenous administration of ricin to Sprague-Dawley rats.
• Collection of serial blood samples up to 48 hours post-exposure.
• Analysis of plasma samples using HILIC and C18 reversed-phase UHPLC-MS, followed by univariate and multivariate statistical analysis.

Main Results:

• Metabolic profiles in blood distinguished ricin-exposed rats from controls before the onset of clinical signs (24 hours).
• 37 metabolites were significantly altered post-ricin exposure.
• A panel of triacylglycerides achieved high diagnostic accuracy (AUROC 0.94-1.0) with increasing numbers of metabolites at 8, 16, and 24 hours.

Conclusions:

• Blood metabolite analysis can serve as a valuable tool for diagnosing and detecting ricin exposure.
• Metabolite biomarkers can facilitate earlier administration of supportive care and future ricin-specific treatments.
• This approach enhances the prognosis for individuals exposed to ricin.