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ABSTRACT: 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.
Journal of Chinese Integrative Medicine 09/2009; 7(8):746-52.
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ABSTRACT: To explore the metabolic effects of acute hypoxia on mice plasma.
Fourteen mice were randomly divided into two groups: control and hypoxia group. The mice of hypoxia group were exposed to a simulated altitude of 6000 meters for 8 hours. Nuclear magnetic resonance spectrometer was used to identify the metabolic changes after acute hypoxia.
Compared with control, the most notable significantly after acute hypoxia exposure. remarkably and lactate increased metabolic changes in plasma were as follows: camrnitine decreased levels of lipids and pyruvate, alanine, taurine, Decreases in levels of beta-HB, ethanol glycerol, glutamate, glycine and serine, and increased choline, glucose, and glutamine were also observed in hypoxia group.
Significant changes in the plasma carbohydrate, lipid and amino acid profiles were observed following acute hypoxia, suggesting a hypoxia-induced alteration in energy and related substances metabolism.
Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology 05/2009; 25(2):177-80.
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ABSTRACT: To study the effect of rifampin (RFP) on the metabonomic profile of rat urine and its relationship with traditional toxicity evaluation of blood biochemical indicators and histopathology.
Thirty-six male Wistar rats were randomly divided into control group, 50 mg/kg RFP group, and 100 mg/kg RFP group, with 12 rats in each group. Rats in each group were given intragastric infusion with a daily dose of 0, 50 mg/kg RFP, and 100 mg/kg RFP for 3, 7, and 14 days, respectively. Then 4 rats in each group were killed on the next day of administration to collect blood samples and liver sample for the determination of blood biochemical indicators and for the pathological analysis of the liver. The urine specimens over 24 hours of each rat were collected before and after each treatment until the rat was killed. 1H nuclear magnetic resonance (1H NMR) spectra of these urine specimens were acquired and subjected to data preprocess and principal component analyses (PCA).
The level of serum total bilirubin of the rat administrated with 100 mg/(kg x d) RFP for 7 days was significantly higher than that of control group (P < 0.05). Mild hepatotoxicity to the rat, treated with RFP of higher dosage (100 mg/kg) and longer duration (14 days), was revealed by the traditional histopathological method. The metabonomic spectra of rat urine in different groups differed from each other; a trajectory bias in determination of rat urine by 1H NMR occurred depending on the administration duration. As demonstrated by 1H NMR spectra of urine in rats treated with RFP, the concentration of urinary citrate and 2-oxoglutarate decreased, along with the remarkable increase of the concentrations of urinary taurine and glucose (compared with those of the control group).
Being consistent with the results of traditional toxicity evaluation measurements, metabonomic method is more sensitive. The 1H-NMR metabonomic profile of the rat urine is closely related with the duration of RFP. The hepatic toxicity induced by RFP is related to the reduction of energy metabolism in tricarboxylic acid cycle and the perturbation of glucose and lipid metabolism.
Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae 12/2008; 30(6):696-702.
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ABSTRACT: To study the effect of different treatment period, of isoniazid (INH) on the metabonomic profile of rat urine and its relationship with traditional toxicity evaluation of blood biochemical indicators and histopathology and to explore the feasibility of metabonomics in the application of drug toxicity.
Sixty male Wistar rats were orally administrated with 0, 50, 100, 200, and 400 mg x kg(-1) INH for 3, 7, and 14 days, respectively. Rat urine was then collected and its 1H nuclear magnetic resonance (NMR) spectra were acquired. All animals underwent traditional toxicity evaluation.
Hepatotoxicity was revealed by traditional toxicity evaluation in rats treated with higher dosage and longer treatment of INH. Time-response relationship existed during the treatment. Time-dependent metabonomics changes conformed with the results of traditional toxicity evaluation. The urine metabonomics showed a trajectory bias from those of the controls or pre-administration, and such bias exaggerated along with the prolongation of treatment, indicating a severer toxic injury. Along with the increase of the concentrations of urinary taurine and glucose and the decrease of the concentrations of urinary citrate and 2-oxoglutarate, the 1H NMR spectra of urine in rats treated with INH also changed.
The metabonomics technique can distinguish the onset and development of toxicity, which helps track and identify biomarkers. The hepatic toxicity induced by INH is related to the injury of mitochondrial function, reduction of energy metabolism in tricarboxylic acid cycle, and perturbations in the metabolism of glucose and lipid. The effect of INH on the rat urine metabonomic profile is related with INH toxicology. Therefore, metabonomics can be recognized as an ideal technique to explore and evaluate the drug toxicities.
Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae 01/2008; 29(6):730-7.
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ABSTRACT: To access the capability of 1H nuclear magnetic resonance (NMR) -based metabonomics in the evaluation of graft function in the perioperation period of liver transplantation.
Plasma samples of 15 male primary hepatic carcinoma patients were collected for clinical biochemical analysis and 1H NMR spectroscopy 1 day before operation, 1 day and 1 week after the operation. The NMR data were analyzed using principal component analysis.
Metabonomic analysis indicated that, compared with those before operation, blood concentrations of valine, alanine, acetone, succinic acid, glutamine, choline, lactate, and glucose increased significantly 1 day after transplantation. One week later, the levels of lipids and choline increased notably, while those of glucose and amino acids decreased. Principal component analysis showed significant difference between metabolic profiles of plasma samples of variant periods of liver transplantation, due to the variation of the levels of glucose, lipids, lactate, and choline. A good agreement was observed between clinical chemistry and metabonomic data.
Metabonomic analysis can clearly identify the difference between the plasma samples of primary hepatic carcinoma patients at different time during the perioperation period of liver transplantation. It therefore may be a promising new technology in predicting the outcomes of liver transplantation.
Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae 01/2008; 29(6):725-9.
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ABSTRACT: The detailed NMR studies and full assignments of the 1H and 13C spectral data for two new furostanol saponins isolated from Agave sisalana leaves are described. Their structures were established using a combination of 1D and 2D NMR techniques including 1H, 13C, 1H-1H COSY, TOCSY, HSQC, HMBC and HSQC-TOCSY, and also FAB-MS spectrometry and chemical methods. The structures were established as (25S)-26-(beta-D-glucopyranosyl)-22 xi-hydroxyfurost-12-one-3beta-yl-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->3)-O-[O-beta-D-glucopyranosyl-(1-->2)]-O-beta-D-glucopyranosyl-(1-->4)-beta-D-galacto- pyranoside (1) and (25S)-26-(beta-D-glucopyranosyl)-22xi-hydroxyfurost-5-en-12-one-3beta-yl-O-alpha-L-rhamno- pyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->3)-O-[O-beta-D-glucopyranosyl-(1-->2)]-O-beta-D-glucopyranosyl- (1-->4)-beta-D-galactopyranoside (2).
Magnetic Resonance in Chemistry 12/2006; 44(12):1090-5. · 1.44 Impact Factor
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ABSTRACT: Ten furostanol saponins were isolated as five pairs of 25R and 25S epimers from the fresh rhizomes of Polygonatum kingianum. Seven of them were identified as new compounds, (25S)-kingianoside D (2), (25S)-kingiano-side C (4), (25R,22)-hydroxylwattinoside C (5), kingianoside E (7), (25S)-kingianoside E (8), kingianoside F (9) and (25S)-kingianoside F (10), together with three known saponins, kingianoside C (1), kingianoside D (3), and 22-hydroxylwattinoside C (6). The structures of the new saponins were determinded by detailed analysis of their 1D and 2D NMR spectra, and by comparison of the spectral data with those reported.
CHEMICAL & PHARMACEUTICAL BULLETIN 08/2006; 54(7):931-5. · 1.59 Impact Factor
