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      Combination of LC/MS and GC/MS based metabolomics to study the hepatotoxic effect of realgar nanoparticles in rats

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          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 −1·d −1 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.

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          Author and article information

          Journal
          CJNM
          Chinese Journal of Natural Medicines
          Elsevier
          1875-5364
          20 September 2017
          : 15
          : 9
          : 684-694
          Affiliations
          1Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), China Pharmaceutical University, Nanjing 210009, China
          2State Key Laboratory of Natural Medicine, China Pharmaceutical University, Nanjing 210009, China
          Author notes
          *Corresponding authors: ZHANG Zun-Jian, Fax/Tel: 86-25-83271454, E-mail: zunjianzhangcpu@ 123456hotmail.com ; HUANG Yin, Tel: 86-25-83271185, E-mail: huangyincpu@ 123456gmail.com .

          These authors have no conflict of interest to declare.

          Article
          S1875-5364(17)30098-5
          10.1016/S1875-5364(17)30098-5
          Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.
          Funding
          Funded by: National Natural Science Foundation of China
          Award ID: 81403181
          Funded by: Basic Research Program of Jiangsu Province
          Award ID: BK20140664
          This work was financially supported by the National Natural Science Foundation of China (No. 81403181) and the Basic Research Program of Jiangsu Province (No. BK20140664).

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