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Urinary metabolomics and biomarkers of aristolochic acid nephrotoxicity by UPLC-QTOF/HDMS
Ying-Yong Zhao1, Dan-Dan Tang, Hua Chen
1Key Laboratory of Resource Biology & Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, No. 229 Taibai North Road, Xi'an, Shaanxi 710069, China.
Background:
Drug-induced nephrotoxicity was one of the most important health problems, with increasing morbidity and mortality. Urinary metabolomics based on ultra performance liquid chromatography coupled with quadrupole time-of-flight high-definition mass spectrometry was applied to aristolochic acid (AA) nephrotoxicity rats to characterize the excretion pathways of endogenous metabolites.
Results:
Compared with the control rats, serum creatinine, serum blood urea nitrogen and urine protein levels were significantly increased in AA nephrotoxicity rats. Metabolomics showed that metabolites including citrate, aconitate, fumarate, glucose, creatinine, p-cresyl sulfate, indoxyl sulfate, hippuric acid, phenylacetylglycine, kynurenic acid, indole-3-carboxylic acid, spermine, uric acid, allantoin, cholic acid and taurine were identified in AA nephrotoxicity rats.
Conclusion:
The identified metabolites suggested that AA nephrotoxicity rats occurred perturbations in Krebs cycle, gut microflora metabolism, amino acid metabolism, purine metabolism and bile acid biosynthesis.
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