Untargeted Urinary Metabolomic Study on Toxicity-alleviation Effect of Huangqi Oral Solution in Cisplatin-exposed Rats
10.11895/j.issn.0253-3820.160800
- VernacularTitle:黄芪口服液降低大鼠顺铂毒性作用机制的尿液代谢组学研究
- Author:
Huiting SONG
;
Changyin LI
;
Yaoyao WAN
;
Xuansheng DING
;
Guoliang DAI
;
Shijia LIU
;
Wenzheng JU
- Keywords:
Huangqi oral solution;
Cisplatin;
Urine;
Metabolomics;
Liquid chromatography-time-of-flight mass spectrometry;
Toxicity
- From:
Chinese Journal of Analytical Chemistry
2017;45(4):565-573
- CountryChina
- Language:Chinese
-
Abstract:
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.
