广防己的肾毒性及代谢组学研究

RichHTML

PDF (PC)

Like

Nephrotoxicity study of Aristolochia fangchi in rats by metabonomics

Abstract

TrendMD

Figures/Tables 4

References 15

Metrics

Comments

Recommended 10

doi:10.3736/jcim20090808

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

Qi Liang, Cheng Ni, Ming Xie, Qi Zhang, Yan-xia Zhang, Xian-zhong Yan, Mei-juan Yang, Shuang-qing Peng . Nephrotoxicity study of Aristolochia fangchi in rats by metabonomics. Journal of Chinese Integrative Medicine, 2009, 7(8): 746-752.

/ Save 0 / Recommend

Add to citation manager EndNote| Reference Manager|ProCite|BibTeX|RefWorks

URL: http://www.jcimjournal.com/EN/10.3736/jcim20090808

http://www.jcimjournal.com/EN/Y2009/V7/I8/746

Table 1

Figure 1

Figure 2

Figure 3

[1]	Vanherweghem JL, Depierreux M, Tielemans C, Abramowicz D, Dratwa M, Jadoul M, Richard C, Vandervelde D, Verbeelen D, Vanhaelen-Fastre R . Rapidly progressive interstitial renal fibrosis in young women: association with slimming regimen including Chinese herbs[J]. Lancet, 1993,341(8842):387-391 doi: 10.1016/0140-6736(93)92984-2
[2]	Nicholson JK, Lindon JC, Holmes E . 'Metabonomics': understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data[J]. Xenobiotica, 1999,29(11):1181-1189 doi: 10.1080/004982599238047
[3]	Lindon JC, Holmes E, Nicholson JK . Pattern recognition methods and applications in biomedical magnetic resonance[J]. Prog NMRS, 2001,39(1):1-40 doi: 10.1016/S0079-6565(00)00036-4
[4]	Nicholson JK, Connelly J, Lindon JC, Holmes E . Metabonomics: a platform for studying drug toxicity and gene function[J]. Nat Rev Drug Discov, 2002,1(2):153-161 doi: 10.1038/nrd728 pmid: 12120097
[5]	Yang CS, Lin CH, Chang SH, Hsu HC . Rapidly progressive fibrosing interstitial nephritis associated with Chinese herbal drugs[J]. Am J Kidney Dis, 2000,35(2):313-318 doi: 10.1016/S0272-6386(00)70343-X pmid: 10676733
[6]	Holmes E, Connor SC, Nicholls AW, Nicholson JK, Lindon JC, Connor SC, Polley S, Connelly J . The identification of novel biomarkers of renal toxicity using automatic data reduction techniques and PCA of proton NMR spectra of urine[J]. Chemometri Intell Lab Sys, 1998,44(1):245-255 doi: 10.1016/S0169-7439(98)00110-5
[7]	Xu B, Zhao YM . Changes of metabonomic profiles of rat urine after oral administration of Radix Gentianae decoction[J]. Zhongguo Yao Li Xue Yu Du Li Xue Za Zhi, 2008,22(3):221-226 doi: 10.3867/j.issn.1000-3002.2008.03.011
	徐斌, 赵毅民 . 大鼠口服龙胆水煎剂后尿液代谢谱的变化[J]. 中国药理学与毒理学杂志, 2008,22(3):221-226 doi: 10.3867/j.issn.1000-3002.2008.03.011
[8]	Nicholson JK, Timbrell JA, Sadler PJ . Proton NMR spectra of urine as indicators of renal damage. Mercury-induced nephrotoxicity in rats[J]. Mol Pharmacol, 1985,27(6):644-651
[9]	Gartland KP, Bonner FW, Nicholson JK . Investigations into the biochemical effects of region-specific nephrotoxins[J]. Mol Pharmacol, 1989,35(2):242-250 pmid: 2918855
[10]	Zhao JY, Yan XZ, Peng SQ . Studying nephrotoxicity of Aristolochia manshuriensis using metabonomics[J]. Shi Jie Ke Xue Ji Shu Zhong Yi Yao Xian Dai Hua, 2007,9(5):54-59, 148
	赵剑宇, 颜贤忠, 彭双清 . 利用代谢组学技术研究中药关木通的肾毒性作用[J]. 世界科学技术: 中医药现代化, 2007,9(5):54-59, 148
[11]	Friese J, Gleitz J, Gutser UT, Heubach JF, Matthiesen T, Wilffert B, Selve N . Aconitum sp. alkaloids: the modulation of voltage-dependent Na+ channels, toxicity and antinociceptive properties[J]. Eur J Pharmacol, 1997,337(2-3):165-174 doi: 10.1016/S0014-2999(97)01268-5
[12]	Wang QJ, Yan XZ, Wu CQ, Zhao JY, Yu SZ, Yuan BL, Liao MY . A nuclear magnetic resonance spectroscopic metabonomics analysis for urine from rats admi-nistrated Z24 orally[J]. Zhongguo Yao Li Xue Yu Du Li Xue Za Zhi, 2004,18(6):460-465
	王全军, 颜贤忠, 吴纯启, 赵剑宇, 余寿忠, 袁本利, 廖明阳 . Z24经口染毒大鼠尿液的核磁共振谱代谢组学研究[J]. 中国药理学与毒理学杂志, 2004,18(6):460-465
[13]	Jaeschke H, Gores GJ, Cederbaum AI, Hinson JA, Pessayre D, Lemasters JJ . Mechanisms of hepatotoxi-city[J]. Toxicol Sci, 2002,65(2):166-176 doi: 10.1093/toxsci/65.2.166
[14]	Liao Y, Peng SQ, Yan XZ, Zhang LS . Metabonomics profile of urine from rats administrated with different treatment period of isoniazid[J]. Zhongguo Yi Xue Ke Xue Xue Bao, 2007,29(6):730-737
	廖艳, 彭双清, 颜贤忠, 张立实 . 抗结核药物异烟肼肝毒性时效关系的代谢组学[J]. 中国医学科学学报, 2007,29(6):730-737
[15]	Ni C . Study on the effect and toxicity of Aristolochiae fangchi, Stephania tetrandra and their combination with Astragali radix separately[M]. Beijing: Beijing University of Chinese Medicine, 2007
	倪诚 . 广防己和粉防己及其配伍黄芪的效毒研究[M]. 北京: 北京中医药大学, 2007

Viewed

Full text

From	Others	local

Times	0	66
Rate	0%	100%

Abstract

148

Just accepted	Online first	Issue

0	0	148

	From	Others

	Times	148
	Rate	100%

Cited

Web of Science	Crossref	ScienceDirect	Search for Citations in Google Scholar >>


This page requires you have already subscribed to WoS.

Shared

Discussed

[1]	Jin-rong Fu. Establishment of multivariate diagnosis and treatment system of modern gynecology of traditional Chinese medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 22-24
[2]	Hao Li, Ming-jiang Yao, Wen-ming Zhao, Jie Guan, Lin-lin Cai, Ling Cui. A randomized, controlled, double-blind trial of Huannao Yicong capsule in senile patients with mild cognitive impairment. Journal of Chinese Integrative Medicine, 2008, 6(1): 25-31
[3]	Zhi-chun Jin. Problems in establishing clinical guideline for integrated traditional Chinese and Western medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 5-8
[4]	SUN Ming-yu, ZUO Jian, DUAN Ji-feng, HAN Jun, FAN Shi-ming, ZHANG Wei, ZHU Li-fang, YAO Ming-hui. Antitumor activities of kushen flavonoids in vivo and in vitro. Journal of Chinese Integrative Medicine, 2008, 6(1): 51-59
[5]	Min Cheng, Qiong Feng, Shu-wen Qian, Hui Gao, Cui-qing Zhu. Preliminary assay of p-amyloid binding elements in heart-beneficial recipe. Journal of Chinese Integrative Medicine, 2008, 6(1): 68-72
[6]	Ning-qun Wang, Liang-duo Jiang, Zong-xing Li. Research progress in asthma-related quality of life. Journal of Chinese Integrative Medicine, 2008, 6(1): 93-97
[7]	Jing-yuan Mao, Chang-xiao Liu, Heng-he Wang, Guang-li Wei , Zhen-peng Zhang, Jie Xing, Wang Xian liang , Ying-fei Bi . Effects of Shenmai Injection on serum concentration and pharmacokinetics of digoxin in dogs with heart failure. Journal of Chinese Integrative Medicine, 2010, 8(11): 1070-1074
[8]	Zhi-mei Wang, Bin Zhang. A study on translation of ellipses in Huangdi Neijing from perspective of hermeneutic theory. Journal of Chinese Integrative Medicine, 2010, 8(11): 1097-1100
[9]	Gui Yu, Jie Wang. Thinking on building the network cardiovasology of Chinese medicine. Journal of Chinese Integrative Medicine, 2012, 10(11): 1206-1210
[10]	Pedro Saganha João, Doenitz Christoph, Greten Tobias, Efferth Thomas, J. Greten Henry. Qigong therapy for physiotherapists suffering from burnout: a preliminary study. Journal of Chinese Integrative Medicine, 2012, 10(11): 1233-1239

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

Just accepted

Online first

Just accepted

Online first