Acta Academiae Medicinae Sinica

Acta Academiae Medicinae Sinica

Acta Academiae Medicinae Sinica ›› 2008, Vol. 30 ›› Issue (6): 696-702.doi: 10.3881/j.issn.1000-503X.2008.06.015

• Original Articles • Previous Articles     Next Articles

Metabonomic Profile of Urine from Rats Administrated with Different Treatment Period of Rifampin

LIAO Yan2;PENG Shuang-qing1;YAN Xian-zhong3;CHEN He-bing3;ZHANG Li-shi4   

  1. 1Research and Evaluation Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing 100071, China 2Department of Rehabilitation, School of Preclinical Medicine, Beijing University of Traditional Chinese Medicine, Beijing 100029, China 3National Center of Biomedical Analysis, Academy of Military Medical Sciences, Beijing 100850, China 4Department of Nutrition and Food Hygiene, West China School of Public Health, Sichuan University, Chengdu 610041, China
  • Received:2008-03-30 Revised:1900-01-01 Online:2008-12-30 Published:2008-12-30
  • Contact: PENG Shuang-qing

Abstract: ABSTRACT:Objective 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. Methods 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). Results The level of serum total bilirubin of the rat administrated with 100 mg/(kg&#8226;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). Conclusions 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.

Key words: metabonomic, nuclear macnetic resonance, pattern recocnition, rifampin, depatotoxicity