title: NMR- and LC-MS/MS-based urine metabolomic investigation of the subacute effects of hexabromocyclododecane in mice.
abstract: In the present study, both untargeted and targeted metabolomics approaches were used to evaluate the subacute effects of hexabromocyclododecane (HBCD) on mice urine metabolome. Untargeted metabolomics based on (1)H NMR showed that HBCD exposure disturbed mice metabolism in both dosed groups, especially in high dosed group. The low-dose HBCD led to a decrease in alanine, malonic acid, and trimethylamine (TMA). High-dose HBCD-treated mice developed high levels of citric acid and 2-ketoglutarate, together with decreased alanine, acetate, formate, TMA, 3-hydroxybutyrate, and malonic acid. Targeted metabolomics for metabolic profiling of 20 amino acids identified alanine, lysine, and phenylalanine as significantly disturbed metabolites. These results indicated that subchronic exposure to HBCD caused a disturbance of mice metabolism, especially in TCA cycle, lipid metabolism, gut microbial metabolism, and homeostasis of amino acids, and the application of untargeted and targeted metabolomics combined with conventional toxicology approaches to evaluate the subacute effects of pollutants will provide more comprehensive information and aid in predicting health risk of these pollutants.
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing, 100193, China.
authors.forename: Dezhen
authors.initials: D
authors.lastname: Wang
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing, 100193, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing, 100193, China.
authors.forename: Xinru
authors.initials: X
authors.lastname: Wang
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing, 100193, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing, 100193, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing, 100193, China. wentaozhu@cau.edu.cn.
authors.forename: Wentao
authors.initials: W
authors.lastname: Zhu
mesh_terms: D000596:Amino Acids; D000818:Animals; D002853:Chromatography, Liquid; D002952:Citric Acid Cycle; D015386:Hazardous Substances / Q000633:toxicity*; D006706:Homeostasis; D006842:Hydrocarbons, Brominated / Q000633:toxicity*; D007656:Ketoglutaric Acids; D050356:Lipid Metabolism / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D055442:Metabolome / Q000502:physiology*; D055432:Metabolomics / Q000379:methods*; D051379:Mice; D053719:Tandem Mass Spectrometry
chemical_list: D000596:Amino Acids; D015386:Hazardous Substances; D006842:Hydrocarbons, Brominated; D007656:Ketoglutaric Acids; C089796:hexabromocyclododecane
keywords: 1H NMR; Amino acids; HBCD; Metabolomics; Urine