Urinary metabolomics study on potential protective and toxic effects of Acanthopanax senticosus harms intervention in rats
10.3760/cma.j.issn.1008-5734.2016.06.005
- VernacularTitle:刺五加干预对大鼠潜在保护/毒性作用的尿代谢组学研究
- Author:
Shuainan ZHANG
1
;
Xuzhao LI
;
Yu WANG
;
Fang LU
;
Shumin LIU
Author Information
1. 黑龙江中医药大学中药毒理学实验室, 哈尔滨,150040
- Publication Type:Journal Article
- Keywords:
ACANTHOPANAX SENTICOSUS;
Metabolomics;
Rats
- From:
Adverse Drug Reactions Journal
2015;(6):415-419
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the potential protective and toxic effects of Acanthopanax senticosus harms(AS)in rats. Methods Twenty male SD rats were divided into the AS-treated and control groups by random number table method. Each group comprised 10 rats. The rats in the AS-treated group were gavage-fed with AS extracts 31. 6 mg/ kg(equivalent to crude drug 0. 386 g/ kg in human)once daily for 20 days and the volume of the drug was 10 ml/ kg. The rats in the control group received an equal volume of saline once daily for 20 days. The urinary samples of 24 h from rats in the 2 groups which were gavage-fed for 1,5,10,15,and 20 days were collected respectively. Ultra-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry was used to detect the ion intensities of metabolites from urinary samples. The ion intensities of urinary metabolites at different time points in the 2 groups were compared. The ion intensity of each metabolite was normalized with respect to the total ion intensities to generate a data matrix. The data matrix at different time points were processed by partial least-squares-discrimination analysis(PLS-DA)of EZinfo software. Characteristic metabolites were screened according to the PLS-DA score plot. Two sets of data matrix with relatively large distance were further processed by orthogonal partial least-squares-discrimination analysis(OPLS-DA)and the variable importance of project(VIP)scores were calculated. Characteristic metabolites induced by AS intervention were screened from variables with VIP > 1 and P < 0. 05 and their mass-charge ratios were detected and compared to the information in Human Metabolome Database(HMDB),and the corresponding metabolites were identified at last. The potential protective or toxic effects of AS in rats represented by these metabolites were analyzed through literature review. Results PLS-DA score plot showed that the urinary metabolic profiles at different time points in the 2 groups had good similarity within groups or time period and presented clustering phenomenon. The urinary metabolic profiles in rats in the 2 groups which were gavage-fed for 1,5,10,15,and 20 days partly overlapped. The urinary metabolic profiles in rats in the AS-treated group with 20 days of AS treatment were far from those in the control group. Two sets of data matrix with relatively large displacement were further processed and 6 potential intervention targets of AS with VIP > 1 and P < 0. 05 were screened and identified as 3-methylguanine,3-methylglutarylcarnitine,3-hydroxydodecanedioic acid, tiglylcarnitine, kynurenic acid,and 13-cis-retinoic acid by comparing with the information of HMDB. At the 20 d of AS-treated group, the expression of 3-methylguanine,kynurenic acid,and 3-hydroxydodecanedioic acid were up-regulated and the expression of tiglylcarnitine,3-hydroxydodecanedioic acid,and 13-cis-retinoic acid were down regulated. By reviewing the related literature,kynurenic acid,13-cis-retinoic acid,and 3-methylguanine may have potential protective effects in rats which were treated with AS and the other 3 metabolites may have potential toxicity. Conclusion The potential intervention effects of AS in rats had two sides,which may have protective effects,and may also have toxic effects.
