TY - JOUR
T1 - Mass spectrometry-based metabolic profiling of rat urine associated with general toxicity induced by the multiglycoside of Tripterygium wilfordii Hook. f.
AU - Chen, Minjun
AU - Ni, Yan
AU - Duan, Hongquan
AU - Qiu, Yunping
AU - Guo, Congying
AU - Jiao, Yang
AU - Shi, Huijuan
AU - Su, Mingming
AU - Jia, Wei
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2008/2
Y1 - 2008/2
N2 - 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.
AB - 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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U2 - 10.1021/tx7002905
DO - 10.1021/tx7002905
M3 - Article
C2 - 18205320
AN - SCOPUS:41649106485
SN - 0893-228X
VL - 21
SP - 288
EP - 294
JO - Chemical research in toxicology
JF - Chemical research in toxicology
IS - 2
ER -