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Citation: SONG Hui-Ting, LI Chang-Yin, WAN Yao-Yao, DING Xuan-Sheng, DAI Guo-Liang, LIU Shi-Jia, JU Wen-Zheng. Untargeted Urinary Metabolomic Study on Toxicity-alleviation Effect of Huangqi Oral Solution in Cisplatin-exposed Rats[J]. Chinese Journal of Analytical Chemistry, ;2017, 45(4): 565-573. doi: 10.11895/j.issn.0253-3820.160800 shu

Untargeted Urinary Metabolomic Study on Toxicity-alleviation Effect of Huangqi Oral Solution in Cisplatin-exposed Rats

1.
Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China;
2.
School of pharmacy, China Pharmaceutical University, Nanjing 211198, China

Received Date: 1 November 2016
Revised Date: 30 December 2016

Fund Project: This work was supported by the National Natural Science Foundation of China (No. 81503300).

A liquid chromatography-quadrupole-time-of-flight mass spectrometer(LC-Q/TOF-MS) based urinary metabolomic approach was employed to assess the toxicity-alleviation effect of Huangqi oral solution(HOs) on cisplatin-exposed rats and explore its possible mechanisms. Rat toxicity model was developed by multiple intraperitoneal injection of low-dose cisplatin, while HOs was orally administrated to rats simultaneously for 16 consecutive days to attenuate or reduce the cisplatin-induced toxicity. 24-hour urine samples on day 18 were collected and analyzed using LC-Q/TOF-MS to obtain the dataset of urinary metabolites. Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were employed to assess the quality of the dataset and screen the potential toxicity-alleviation biomarkers. The serum level of rat creatinine and urea nitrogen on day 20 was determined, and the results showed that successive administration of HOs significantly reduced the cisplatin-induced increase of creatinine and urea nitrogen. PCA cluster analysis clearly demonstrated that HOs could partly improve the CDDP-induced abnormality of metabolic profiling. 35 urinary metabolites were finally screened as the potential biomarkers associated with the toxicity-attenuation effect of HOs, according to the combination of the analysis results of OPLS-DA, t-test and fold change analysis. Further metabolic pathway analysis revealed that HOs could restore the metabolic disorders of amino acid, energy and nucleotide, thereby exerted its toxicity-alleviation effect.
- Huangqi oral solution,
- Cisplatin,
- Urine,
- Metabolomics,
- Liquid chromatography-time-of-flight mass spectrometry,
- Toxicity
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