title: Metabolic profiling reveals disorder of carbohydrate metabolism in mouse fibroblast cells induced by titanium dioxide nanoparticles.
abstract: As titanium dioxide (TiO(2)) nanoparticles are widely used commercially, their potential biosafety and metabolic mechanism needs to be fully explained. In this study, the cytotoxicity of homogeneous and weakly aggregated (< 100 nm) TiO(2) nanoparticles was investigated by analyzing the changes in metabolite profiles both in mouse fibroblast (L929) cells and their corresponding culture media using gas chromatograph with a time-of-flight mass spectrometry (GC/TOFMS)-based metabolomic strategy. With multivariate statistics analysis, satisfactory separations were observed in principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models. Based on the variable importance in the OPLS-DA models, a series of differential metabolites were identified by comparison between TiO(2) nanoparticle-treated L929 cells or their corresponding culture media and the control groups. It was found that the major biochemical metabolism (carbohydrate metabolism) was suppressed in TiO(2) nanoparticle-treated L929 cells and their corresponding culture media. These results might account for the serious damage to energy metabolism in mitochondria and the increased cellular oxidation stress in TiO(2) nanoparticle-induced L929 cells. These results also suggest that the metabolomic strategy had a great potential in evaluating the cytotoxicity of TiO(2) nanoparticles and thus was very helpful in understanding its underlying molecular mechanisms.
authors.affiliation: Instrumental Analysis Center, Shanghai Jiao Tong University, 800 Dongchuan Road, 200240, Shanghai, China; Shanghai 9th People's Hospital, School of Medicine, Shanghai Jiao Tong University, 639 Zhizaoju Road, 200011, Shanghai, China.
authors.forename: Chengyu
authors.initials: C
authors.lastname: Jin
authors.forename: Yumin
authors.initials: Y
authors.lastname: Liu
authors.forename: Limin
authors.initials: L
authors.lastname: Sun
authors.forename: Tianlu
authors.initials: T
authors.lastname: Chen
authors.forename: Yinan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Aihua
authors.initials: A
authors.lastname: Zhao
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.forename: Melanie
authors.initials: M
authors.lastname: Cristau
authors.forename: Kaisheng
authors.initials: K
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
mesh_terms: D000818:Animals; D050260:Carbohydrate Metabolism / Q000187:drug effects*; D018929:Cell Culture Techniques; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008401:Gas Chromatography-Mass Spectrometry; D016018:Least-Squares Analysis; D055442:Metabolome / Q000187:drug effects*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000633:toxicity*; D025341:Principal Component Analysis; D014025:Titanium / Q000633:toxicity*
chemical_list: C009495:titanium dioxide; D014025:Titanium