ArticleMetabolomics : Official journal of the Metabolomic Society2019
Multiple metabolic pathways are predictive of ricin intoxication in a rat model.
Article in Metabolomics : Official journal of the Metabolomic Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 9 citations in OpenAlex.
- Derivation of metabolic point of departure using high-throughput in vitro metabolomics: investigating the importance of sampling time points on benchmark concentration values in the HepaRG cell line.Archives of toxicology · 2023Article
- Distinct Metabolic States Are Observed in Hypoglycemia Induced in Mice by Ricin Toxin or by Fasting.Toxins · 2022Article
- Approaches in metabolomics for regulatory toxicology applications.The Analyst · 2021Review
- Liquid Chromatography-Mass Spectrometry for Clinical Metabolomics: An Overview.Advances in experimental medicine and biology · 2021Article
- Assessment of human plasma and urine sample preparation for reproducible and high-throughput UHPLC-MS clinical metabolic phenotyping.The Analyst · 2020Article
- Toxicometabolomics of the new psychoactive substances α-PBP and α-PEP studied in HepaRG cell incubates by means of untargeted metabolomics revealed unexpected amino acid adducts.Archives of toxicology · 2020Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
introductionExposure 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.
objectivesTo determine time-dependent metabolic changes in Sprague-Dawley rats following intravenous exposure to ricin.
methodsSprague-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 C
resultsIn 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.
conclusionsThese 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.
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