Combination of LC/MS and GC/MS based metabolomics to study the hepatotoxic effect of realgar nanoparticles in rats.
10.1016/S1875-5364(17)30098-5
- Author:
Mo-Han ZHANG
1
;
Jia-Qing CHEN
1
;
Hui-Min GUO
1
;
Rui-Ting LI
1
;
Yi-Qiao GAO
1
;
Yuan TIAN
1
;
Zun-Jian ZHANG
2
,
3
;
Yin HUANG
4
Author Information
1. Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), China Pharmaceutical University, Nanjing 210009, China.
2. Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), China Pharmaceutical University, Nanjing 210009, China
3. State Key Laboratory of Natural Medicine, China Pharmaceutical University, Nanjing 210009, China. Electronic address: zunjianzhangcpu@hotmail.com.
4. Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), China Pharmaceutical University, Nanjing 210009, China. Electronic address: huangyincpu@gmail.com.
- Publication Type:Journal Article
- Keywords:
Hepatotoxicity;
Liver extracts;
Metabolomics;
Realgar nanoparticles
- MeSH:
Animals;
Biomarkers;
blood;
chemistry;
Chromatography, Liquid;
methods;
Fatty Acids;
metabolism;
Gas Chromatography-Mass Spectrometry;
methods;
Liver;
chemistry;
drug effects;
metabolism;
Male;
Mass Spectrometry;
methods;
Metabolomics;
methods;
Nanoparticles;
toxicity;
Rats;
Rats, Sprague-Dawley;
Triglycerides;
metabolism
- From:
Chinese Journal of Natural Medicines (English Ed.)
2017;15(9):684-694
- CountryChina
- Language:English
-
Abstract:
Realgar nanoparticles (NPs) are increasingly used as therapeutic agents for their enhanced anti-proliferation effect and cytotoxicity on cancer cells. However, the alteration of particle size may enhance biological reactivity as well as toxicity. A LC/MS and GC/MS based metabolomics approach was employed to explore the mechanism of realgar NPs-induced hepatotoxicity and identify potential biomarkers. Male Sprague-Dawley rats were administrated intragastrically with realgar or realgar NPs at a dose of 1.0 g·kg·d for 28 days and toxic effects of realgar NPs on liver tissues were examined by biochemical indicator analysis and histopathologic examination. Increased levels of serum enzymes and high hepatic steatosis were discovered in the realgar NPs treated group. Multivariate data analysis revealed that rats with realgar NPs-induced hepatotoxicity could be distinctively differentiated from the animals in the control and realgar treated groups. In addition, 21 and 32 endogenous metabolites were apparently changed in the serum and live extracts, respectively. Realgar NPs might induce free fatty acid and triglyceride accumulation, resulting in hepatotoxicity. In conclusion, the present study represents the first comprehensive LC/MS- and GC/MS-based metabolomics analysis of realgar NPs-induced hepatotoxicity, which may help further research of nanotoxicity.
