Aristolochic acid induced changes in the metabolic profile of rat urine

Prolonged exposure to aristolochic acid (AA) has shown to pose rapid progressive renal fibrosis in Belgium women in a slimming regimen in the early 90s. We hypothesize that changes in metabolic profile could have occurred before symptoms were observed, which may allow early treatment. In this study, metabonomics was used for toxicology study of AA in rats. Liquid chromatography coupled with a hybrid quadrupole time-of-flight mass spectrometry (Qq-TOF) was used for the analysis of endogenous metabolites in rat urine samples. The difference in metabolic profiles between the control and the dosed rats was well observed by the principal component analysis (PCA) of the MS data. Significant changes of two metabolite markers, kynurenic acid and hippuric acid, were detected in the rat urine samples. The identification of potential biomarkers was performed by high-resolution mass measurement and MS-MS analyses on a Qq-TOF. We believe that metabolic profiling may act as a preclinical protocol for AA exposure before symptoms are observed.