We propose here a combined gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS) metabolic profiling strategy to elucidate the toxicity in rats induced by orally administered multiglycosides of Tripterygium wilfordii Hook. f. (GTW) in multiple organs including the kidney, liver, and testis. Overnight 12-h urine samples were collected from Sprague-Dawley male rats exposed to GTW (100 mg/kg/day, n = 6) and healthy controls (n = 6) at predose and at the 1st, 3rd, 6th, 10th, and 14th day postdose for both GC/MS and LC/MS analyses. The integrated urinary MS data were analyzed via multivariate statistical techniques such as principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) to identify the differential metabolites and pertinent altered biological pathways in response to the herbal toxin. The liver, kidney, and testis were also assessed using conventional histopathological examinations at the end point of the experiment. This work indicates that GTW caused a time-dependent toxic effect at a high dose as revealed by the perturbed metabolic regulatory network involving disorders in energy metabolism, elevated amino acid and choline metabolism pathways, as well as altered structure of gut flora. This integrated MS-based metabolic profiling approach has been able to capture and probe the metabolic alterations associated with the onset and progression of multiorgan toxicity induced by GTW, thereby permitting a comprehensive understanding of systemic toxicity for phytochemicals and other types of xenobiotic agents.
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