Integrative Metabolomics, Proteomics and Transcriptomics Analysis Reveals Liver Toxicity of Mesoporous Silica Nanoparticles
As pharmaceutical excipients, mesoporous silica nanoparticles (MSNs) have attracted considerable concern based on potential risks to the public. The impact of MSNs on biochemical metabolism is poorly understood, and few studies have compared the effects of MSNs administered via different routes. To...
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.835359/full |
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| author | Jing Li Runbin Sun Hui Xu Hui Xu Guangji Wang |
| author_facet | Jing Li Runbin Sun Hui Xu Hui Xu Guangji Wang |
| author_sort | Jing Li |
| collection | DOAJ |
| description | As pharmaceutical excipients, mesoporous silica nanoparticles (MSNs) have attracted considerable concern based on potential risks to the public. The impact of MSNs on biochemical metabolism is poorly understood, and few studies have compared the effects of MSNs administered via different routes. To evaluate the hepatotoxicity of MSNs, metabolomics, proteomics and transcriptomic analyses were performed in mice after intravenous (20 mg/kg/d) or oral ad-ministration (200 mg/kg/d) of MSNs for 10 days. Intravenous injection induced significant hepatic injury based on pathological inspection and increased the levels of AST/ALT and the inflammatory factors IL-6, IL-1β and TNF-a. Omics data suggested intravenous administration of MSNs perturbed the following metabolites: succinate, hypoxanthine, GSSG, NADP+, NADPH and 6-phosphogluconic acid. In addition, increases in GPX, SOD3, G6PD, HK, and PFK at proteomic and transcriptomic levels suggested elevation of glycolysis and pentose phosphate pathway, synthesis of glutathione and nucleotides, and antioxidative pathway activity, whereas oxidative phosphorylation, TCA and mitochondrial energy metabolism were reduced. On the other hand, oral administration of MSNs disturbed inflammatory factors and metabolites of ribose-5-phosphate, 6-phosphogluconate, GSSG, and NADP+ associated with the pentose phosphate pathway, glutathione synthesis and oxidative stress albeit to a lesser extent than intravenous injection despite the administration of a ten-fold greater dose. Overall, systematic biological data suggested that intravenous injection of nanoparticles of pharmaceutical excipients substantially affected hepatic metabolism function and induced oxidative stress and inflammation, whereas oral administration exhibited milder effects compared with intravenous injection. |
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| last_indexed | 2024-12-17T18:38:35Z |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-197f405a1a5e4f2ba488174421088fe12022-12-21T21:37:01ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-01-011310.3389/fphar.2022.835359835359Integrative Metabolomics, Proteomics and Transcriptomics Analysis Reveals Liver Toxicity of Mesoporous Silica NanoparticlesJing Li0Runbin Sun1Hui Xu2Hui Xu3Guangji Wang4Lab of Nano-Biology Technology, School of Physics and Electronics, Institute of Super-Microstructure and Ultrafast Process in Advanced Materials, Central South University, Changsha, ChinaKey Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, ChinaLab of Nano-Biology Technology, School of Physics and Electronics, Institute of Super-Microstructure and Ultrafast Process in Advanced Materials, Central South University, Changsha, ChinaKey Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, ChinaKey Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, ChinaAs pharmaceutical excipients, mesoporous silica nanoparticles (MSNs) have attracted considerable concern based on potential risks to the public. The impact of MSNs on biochemical metabolism is poorly understood, and few studies have compared the effects of MSNs administered via different routes. To evaluate the hepatotoxicity of MSNs, metabolomics, proteomics and transcriptomic analyses were performed in mice after intravenous (20 mg/kg/d) or oral ad-ministration (200 mg/kg/d) of MSNs for 10 days. Intravenous injection induced significant hepatic injury based on pathological inspection and increased the levels of AST/ALT and the inflammatory factors IL-6, IL-1β and TNF-a. Omics data suggested intravenous administration of MSNs perturbed the following metabolites: succinate, hypoxanthine, GSSG, NADP+, NADPH and 6-phosphogluconic acid. In addition, increases in GPX, SOD3, G6PD, HK, and PFK at proteomic and transcriptomic levels suggested elevation of glycolysis and pentose phosphate pathway, synthesis of glutathione and nucleotides, and antioxidative pathway activity, whereas oxidative phosphorylation, TCA and mitochondrial energy metabolism were reduced. On the other hand, oral administration of MSNs disturbed inflammatory factors and metabolites of ribose-5-phosphate, 6-phosphogluconate, GSSG, and NADP+ associated with the pentose phosphate pathway, glutathione synthesis and oxidative stress albeit to a lesser extent than intravenous injection despite the administration of a ten-fold greater dose. Overall, systematic biological data suggested that intravenous injection of nanoparticles of pharmaceutical excipients substantially affected hepatic metabolism function and induced oxidative stress and inflammation, whereas oral administration exhibited milder effects compared with intravenous injection.https://www.frontiersin.org/articles/10.3389/fphar.2022.835359/fullmesoporous silica nanoparticlemetabolomicsproteomicstranscriptomichepatotoxicityoxidative stress |
| spellingShingle | Jing Li Runbin Sun Hui Xu Hui Xu Guangji Wang Integrative Metabolomics, Proteomics and Transcriptomics Analysis Reveals Liver Toxicity of Mesoporous Silica Nanoparticles Frontiers in Pharmacology mesoporous silica nanoparticle metabolomics proteomics transcriptomic hepatotoxicity oxidative stress |
| title | Integrative Metabolomics, Proteomics and Transcriptomics Analysis Reveals Liver Toxicity of Mesoporous Silica Nanoparticles |
| title_full | Integrative Metabolomics, Proteomics and Transcriptomics Analysis Reveals Liver Toxicity of Mesoporous Silica Nanoparticles |
| title_fullStr | Integrative Metabolomics, Proteomics and Transcriptomics Analysis Reveals Liver Toxicity of Mesoporous Silica Nanoparticles |
| title_full_unstemmed | Integrative Metabolomics, Proteomics and Transcriptomics Analysis Reveals Liver Toxicity of Mesoporous Silica Nanoparticles |
| title_short | Integrative Metabolomics, Proteomics and Transcriptomics Analysis Reveals Liver Toxicity of Mesoporous Silica Nanoparticles |
| title_sort | integrative metabolomics proteomics and transcriptomics analysis reveals liver toxicity of mesoporous silica nanoparticles |
| topic | mesoporous silica nanoparticle metabolomics proteomics transcriptomic hepatotoxicity oxidative stress |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.835359/full |
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