Orthologous metabonomic qualification of a rodent model combined with magnetic resonance imaging for an integrated evaluation of the toxicity of Hypochoeris radicata.

In the present study, we have used metabonomics combined with magnetic resonance imaging (MRI) to investigate an orphan neurological disease, Australian stringhalt, described in horse-ingesting inflorescences of Hypochoeris radicata (HR), without any knowledge on the toxic principle and without any practical possibility to perform experiments on the target species. To get valuable candidate biomarkers, we have chosen the mouse species as a "metabolically competent" laboratory animal model. Metabonomics has been applied as a holistic approach to obtain some pertinent metabolic information about the target organs and biomarker metabolites involved in the HR-induced disruptive events. From urine, liver, and brain metabolic fingerprints, HR ingestion induced a very significant effect on the general metabolism, which is proportional to the HR dose administered and to the HR intoxication duration. The main metabolic biomarker in the mouse model of an intoxication specifically induced by HR feeding has been unambiguously identified as scyllo-inositol. A significant increase of this metabolic marker has been measured in urine and in hydrosoluble liver or brain extracts with a very significant canonical link between these two organs. MRI results obtained in the thalamus have confirmed the involvement of scyllo-inositol, a metabolite found in many neurodegenerative diseases, in some specific metabolic disruptions involved in both neuronal and glial dysfunctions as awaited from etiology of this horse disease. This brain metabolic biomarker has been clearly associated with changes in N-acetyl-aspartate, lactate, and choline cerebral concentration found in both neuronal and glial dysfunctions. Scyllo-inositol is a valuable candidate biomarker of the Australian stringhalt disease that needs now to be clinically validated in the target species.