NDLI: Gas chromatography time-of-flight mass spectrometry based metabolomic approach to evaluating toxicity of triptolide

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Ask not what data standards can do for you but what you can do for data standards: a personal view of reporting standardisation in metabolomic experiments

Metabolomics : Volume 7, Issue 1, March 2011

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Gas chromatography time-of-flight mass spectrometry based metabolomic approach to evaluating toxicity of triptolide

Content Provider	Springer Nature Link
Author	Aa, Jiye Shao, Feng Wang, Guangji Huang, Qing Zha, Weibin Yan, Bei Zheng, Tian Liu, Linsheng Cao, Bei Shi, Jian Li, Mengjie Zhao, Chunyan Wang, Xinwen Wu, Zimei
Copyright Year	2010
Abstract	Metabolomics allows high-throughput analysis of low-molecular-weight compounds in biofluids that reflect the physiological status and biochemical metabolism of living systems. Hence it has the potential to evaluate toxicity and clarifies the metabolism-related toxic mechanisms. In this study a promising candidate drug parent, triptolide, was given to Sprague–Dawley rats as a model toxicant at a single dose of 0.6, or 2.4 mg/kg, i.g. Both routine biochemical assays and histopathological inspection showed time-dependent hepatic toxicity at the higher dose, but no obvious toxicity at the lower dose. Meanwhile, serum metabolome was profiled using the non-targeted metabolomic tool, gas chromatography time-of-flight mass spectrometry. Based on the acquired metabolomic data, mathematical models were calculated and the metabolic patterns of serum were evaluated using projection to latent structure-discriminant analysis. The relative distance of each treated group from the normal control was calculated to provide a measure of toxicity. Treatment with triptolide at either the higher or lower dose caused deviations in the metabolic pattern and resulted in perturbation of taurine, creatinine, free fatty acids, β-hydroxybutyrate, tricarboxylic acid cycle intermediates, and amino acids. This finding indicates the dysfunction of β-oxidation of free fatty acids and impairment of the mitochondria and confirms the hepatic toxicity of triptolide. The identified toxic markers and the calculated relative distance values quantitatively demonstrated dose- and time-dependent toxicity, whereas the scores plot of the model provided the qualitative information. The metabolomic approach was non-invasive and more sensitive than routine toxic assessment, and the results of both methods correlated well.
Starting Page	217
Ending Page	225
Page Count	9
File Format	PDF
ISSN	15733882
Journal	Metabolomics
Volume Number	7
Issue Number	2
e-ISSN	15733890
Language	English
Publisher	Springer US
Publisher Date	2010-09-25
Publisher Institution	Metabolomics Society
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Projection to latent structure-discriminant analysis Toxicity Metabolomics Relative distance method Triptolide Molecular Medicine Developmental Biology Cell Biology Biomedicine general Biochemistry
Content Type	Text
Resource Type	Article
Subject	Endocrinology, Diabetes and Metabolism Clinical Biochemistry Biochemistry

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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