Metabolomic analysis characterizes tissue specific indomethacin-induced metabolic perturbations of rats

Lv, Haitao, Liu, Lian, Palacios, Gustavo, & Chen, Xi (2011) Metabolomic analysis characterizes tissue specific indomethacin-induced metabolic perturbations of rats. The Analyst, 136(11), pp. 2260-2269.

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In this study, the promising metabolomic approach integrating with ingenuity pathway analysis (IPA) was applied to characterize the tissue specific metabolic perturbation of rats that was induced by indomethacin. The selective pattern recognition analyses were applied to analyze global metabolic profiling of urine of rats treated by indomethacin at an acute dosage of reference that has been proven to induce tissue disorders in rats, evaluated throughout the time-course of -24-72 h. The results preliminarily revealed that modifications of amino acid metabolism, fatty acid metabolism and energetically associated metabolic pathways accounted for metabolic perturbation of the rats that was induced by indomethacin. Furthermore, IPA was applied to deeply analyze the biomarkers and their relations with the metabolic perturbations evidenced by pattern recognition analyses. Specific biochemical functions affected by indomethacin suggested that there is an important correlation of its effects in kidney and liver metabolism, based on the determined metabolites and their pathway-based analysis. The IPA correlation of the three major biomarkers, identified as creatinine, prostaglandin E2 and guanosine, suggested that the administration of indomethacin induced certain levels of toxicity in the kidneys and liver. The changes in the levels of biomarker metabolites allowed the phenotypical determination of the metabolic perturbations induced by indomethacin in a time-dependent manner.

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ID Code: 62105
Item Type: Journal Article
Refereed: Yes
Keywords: Animals, Biological Markers/urine, Chromatography, High Pressure Liquid/*methods, Creatinine/urine, Dinoprostone/urine, Guanosine/urine, Indomethacin/*pharmacology, Kidney/drug effects/metabolism, Liver/drug effects/metabolism, Mass Spectrometry/*methods, *Metabolome, Principal Component Analysis, Rats, Sprague-Dawley, Time Factors
DOI: 10.1039/c1an15126f
ISSN: 1364-5528
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 02 Sep 2013 23:10
Last Modified: 05 Sep 2013 02:54

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