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Journal of Chinese Integrative Medicine ›› 2009, Vol. 7 ›› Issue (8): 746-752.doi: 10.3736/jcim20090808

• Original Experimental Research • Previous Articles     Next Articles

Nephrotoxicity study of Aristolochia fangchi in rats by metabonomics

Qi Lianga,Cheng Nia,Ming Xiea,Qi Zhangb,Yan-xia Zhanga,Xian-zhong Yanb,Mei-juan Yanga,Shuang-qing Penga   

  1. a Department of Formulaology, Beijing University of Chinese Medicine, Beijing 100029, China
    b National Center of Biomedical Analysis，Beijing 100850，China
  • Received:2009-04-22 Accepted:2009-06-20 Online:2009-08-20 Published:2009-08-15
  • Contact: Ming Xie E-mail:xieming603@263.net

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Objective

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

Methods

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 1H 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. Results

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.
Conclusion

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.

Key words: Aristolochia fangchi, Nephrotoxicity, Metabonomics, Nuclear magnetic resonance, Pattern recognition, Rats

Table 1

Contents of BUN and SCr of rats in two groups on different time-points ($\bar{x}$±s, mmol/L)"

Group n BUN SCr
Normal control
Before treatment 8 4.12±0.42 30.20±4.32
After 2-week treatment 8 6.30±0.33 41.80±5.81
After 4-week treatment 8 5.58±1.06 50.40±4.83
2 weeks after treatment 8 5.82±0.65 56.40±3.78
Aristolochia fangchi
Before treatment 8 4.12±0.42 30.20±4.32
After 2-week treatment 8 7.58±0.80* 37.25±3.24
After 4-week treatment 8 13.67±2.18** 80.63±13.78**
2 weeks after treatment 8 13.63±1.44** 65.25±12.36

Figure 1

Renal histopathological changes of rats at different time-points (HE staining, ×400) A: Normal control group; B: Aristolochia fangchi group, after 2-week administration; C: Aristolochia fangchi group, after 4-week administration; D: Aristolochia fangchi group, 2 weeks after administration."

Figure 2

1H NMR spectra of rats treated with Aristolochia fangchi after different treatment days a: Before administration; b: After 2-week administration; c: After 4-week administration; d: Two weeks after administration."

Figure 3

Pattern recognition and corresponding loading plots of urine samples obtained from rats in normal control group and Aristolochia fangchi group A: PLS-DA score scatter and corresponding loading plots; B: PCA score scatter and corresponding loading plots; C: PCA score scatter and corresponding loading plots. Z: Normal control group; G: Aristolochia fangchi group; a: Before administration; b: After 2-week administration; c: After 4-week administration; d: Two weeks after administration."

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