[Nephrotoxicity study of Aristolochia fangchi in rats by metabonomics]

To study the changes of metabolites in rat urine after treatment of Aristolochia fangchi decoction by metabonomic method.

Sixty-four male SD rats were divided into Aristolochia fangchi group and normal control group. Rats in the Aristolochia fangchi group were orally administered with 8.1 g/(kg.d) of Aristolochia fangchi and the normal control group was administered with equal volume of distilled water for 4 weeks. Twenty-four hour urine was collected at different time points (before, after 2- and 4-week administration and 2 weeks after administration) and their H nuclear magnetic resonance (NMR) spectra were acquired and subjected to data process, including principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) or orthogonal signal correction (OSC). The contents of blood urea nitrogen (BUN) and serum creatinine (SCr) and histopathological changes of the renal tissues were also detected.

The content of BUN of the Aristolochia fangchi group was markedly higher than that of the normal control group after 2-week administration (P<0.05), and cellular edema in tubular endothelial cells, structure damage of glomeruli and inflammatory cell infiltration were found in the kidney. Along with the lasting of administration to 4-week, the renal injury in the Aristolochia fangchi group became more serious, and the contents of BUN and SCr were all significantly higher as compared with the normal control group (P<0.05). Two weeks after administration, the content of BUN in the Aristolochia fangchi group was still higher than that in the normal control group (P<0.05), and the pathological changes in renal tissues were not different from those on the 4th week. The urine of the Aristolochia fangchi group could be readily discriminated from the normal control group at every time point based on PCA. During the whole administration period, compared with the normal control group, the concentration of urinary taurine was increased time-dependently, while the citrate was decreased in the Aristolochia fangchi group. The concentration of hippurate was increased at the 2nd week and the 6th week (2 weeks after drug withdrawal) but decreased at the 4th week; the concentration of creatinine/creatine was increased at the 4th week but decreased at the 6th week; the concentration of 2-oxo-glutarate was decreased and the concentration of trimethylamine oxide was increased at the 4th and 6th week.

High-dose Aristolochia fangchi can induce renal lesion and its seriousness is correspondent to the lasting of administration. Aristolochia fangchi may also have toxicity on liver.