title: UHPLC-Q-TOF/MS based plasma metabolomics reveals the metabolic perturbations by manganese exposure in rat models.
abstract: Although manganese (Mn) is an essential metal ion biological cofactor, high concentrations could potentially induce an accumulation in the brain and lead to manganism. However, there is no "gold standard" for manganism assessment due to a lack of objective biomarkers. We hypothesized that Mn-induced alterations are associated with metabolic responses to manganism. Here we use an untargeted metabolomics approach by performing ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) on control and Mn-treated rat plasma, to identify metabolic disruptions under high Mn exposure conditions. Sprague-Dawley rats had access to deionized drinking water that was either Mn-free or contained 200 mg Mn per L for 5 weeks. Mn-exposure significantly increased liver Mn concentration in comparison with the control, and also resulted in extensive necrosis and dissolved nuclei, which suggested liver damage from hepatic histopathology. Principal component analysis readily distinguished the metabolomes between the control group and the Mn-treated group. Using multivariate and univariate analysis, Mn significantly altered the concentrations of 36 metabolites (12 metabolites showed a remarkable increase in number and 24 metabolites reduced significantly in concentration) in the plasma of the Mn-treated group. Major alterations were observed for purine metabolism, amino acid metabolism and fatty acid metabolism. These data provide metabolic evidence and putative biomarkers for the Mn-induced alterations in plasma metabolism. The targets of these metabolites have the potential to improve our understanding of cell-level Mn trafficking and homeostatic mechanisms.
authors.affiliation: College of Veterinary Medicine, Northwest A & F University, Yangling 712100, China. zyh19620207@163.com and Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Agro-Products Processing Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
authors.forename: Zhiqi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China.
authors.forename: Shengyi
authors.initials: S
authors.lastname: Wang
authors.affiliation: Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China.
authors.forename: Dongan
authors.initials: D
authors.lastname: Cui
authors.affiliation: College of Veterinary Medicine, Northwest A & F University, Yangling 712100, China. zyh19620207@163.com.
authors.forename: Xinke
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou 730050, China.
authors.forename: Yongming
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Veterinary Medicine, Northwest A & F University, Yangling 712100, China. zyh19620207@163.com.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood*; D001921:Brain / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D008297:Male; D008345:Manganese / Q000494:pharmacology*; D053858:Metabolic Networks and Pathways / Q000187:drug effects*; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D015415:Biomarkers; D008345:Manganese