PMID- 33662726 OWN - NLM STAT- MEDLINE DCOM- 20210513 LR - 20210513 IS - 1879-1298 (Electronic) IS - 0045-6535 (Linking) VI - 275 DP - 2021 Jul TI - Oxidative stress- and mitochondrial dysfunction-mediated cytotoxicity by silica nanoparticle in lung epithelial cells from metabolomic perspective. PG - 129969 LID - S0045-6535(21)00438-0 [pii] LID - 10.1016/j.chemosphere.2021.129969 [doi] AB - Quantities of researches have demonstrated silica nanoparticles (SiNPs) exposure inevitably induced damage to respiratory system, nonetheless, knowledge of its toxicological behavior and metabolic interactions with the cellular machinery that determines the potentially deleterious outcomes are limited and poorly elucidated. Here, the metabolic responses of lung bronchial epithelial cells (BEAS-2B) under SiNPs exposure were investigated using ultra performance liquid chromatography-mass spectrum (UPLC-MS)-based metabolomics research. Results revealed that even with low cytotoxicity, SiNPs disturbed global metabolism. Five metabolic pathways were significantly perturbed, in particular, oxidative stress- and mitochondrial dysfunction-related GSH metabolism and pantothenate and coenzyme A (CoA) biosynthesis, where the identified metabolites glutathione (GSH), glycine, beta-alanine, cysteine, cysteinyl-glycine and pantothenic acid were included. In support of the metabolomics profiling, SiNPs caused abnormality in mitochondrial structure and mitochondrial dysfunction, as evidenced by the inhibition of cellular respiration and ATP production. Moreover, SiNPs triggered oxidative stress as confirmed by the dose-dependent ROS generation, down-regulated nuclear factor erythroid 2-related factor 2 (NRF2) signaling, together with GSH depletion in SiNPs-treated BEAS-2B cells. Oxidative DNA damage and cell membrane dis-integrity were also detected in response to SiNPs exposure, which was correspondingly in agreed with the elevated 8-hydroxyguanosine (8-OHdG) and decreased phospholipids screened through metabolic analysis. Thereby, we successfully used the metabolomics approaches to manifest SiNPs-elicited toxicity through oxidative stress, mitochondrial dysfunction, DNA damage and rupture of membrane integrity in BEAS-2B cells. Overall, our study provided novel insights into the mechanism underlying SiNPs-induced pulmonary toxicity. CI - Copyright (c) 2021. Published by Elsevier Ltd. FAU - Zhao, Xinying AU - Zhao X AD - Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China. FAU - Abulikemu, Alimire AU - Abulikemu A AD - Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China; Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing, 100069, China. FAU - Lv, Songqing AU - Lv S AD - Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China. FAU - Qi, Yi AU - Qi Y AD - Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China; Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing, 100069, China. FAU - Duan, Junchao AU - Duan J AD - Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China; Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing, 100069, China. FAU - Zhang, Jie AU - Zhang J AD - State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, 361102, Xiamen, China. FAU - Chen, Rui AU - Chen R AD - Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China. FAU - Guo, Caixia AU - Guo C AD - Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China; Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing, 100069, China. Electronic address: guocx@ccmu.edu.cn. FAU - Li, Yanbo AU - Li Y AD - Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China. Electronic address: ybli@ccmu.edu.cn. FAU - Sun, Zhiwei AU - Sun Z AD - Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, China. LA - eng PT - Journal Article DEP - 20210215 PL - England TA - Chemosphere JT - Chemosphere JID - 0320657 RN - 7631-86-9 (Silicon Dioxide) SB - IM MH - Chromatography, Liquid MH - Epithelial Cells/metabolism MH - Lung MH - Metabolomics MH - Mitochondria/metabolism MH - *Nanoparticles/toxicity MH - Oxidative Stress MH - *Silicon Dioxide/metabolism/toxicity MH - Tandem Mass Spectrometry OTO - NOTNLM OT - Cytotoxicity OT - Metabolomic OT - Mitochondrial dysfunction OT - Oxidative stress OT - Silica nanoparticle COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2021/03/05 06:00 MHDA- 2021/05/14 06:00 CRDT- 2021/03/04 20:16 PHST- 2020/11/25 00:00 [received] PHST- 2021/02/07 00:00 [revised] PHST- 2021/02/08 00:00 [accepted] PHST- 2021/03/05 06:00 [pubmed] PHST- 2021/05/14 06:00 [medline] PHST- 2021/03/04 20:16 [entrez] AID - S0045-6535(21)00438-0 [pii] AID - 10.1016/j.chemosphere.2021.129969 [doi] PST - ppublish SO - Chemosphere. 2021 Jul;275:129969. doi: 10.1016/j.chemosphere.2021.129969. Epub 2021 Feb 15.