title: GC-TOF/MS-based metabolomic strategy for combined toxicity effects of deoxynivalenol and zearalenone on murine macrophage ANA-1 cells.
abstract: The actual health risk from exposure to combined mycotoxins is unknown, and few studies have focused on changes to cellular biological systems (e.g., metabolomics) caused by combined mycotoxic effects. To evaluate the combined mycotoxic effects of deoxynivalenol (DON) and zearalenone (ZEN) on the level of cellular biological systems, gas chromatographic, time-of-flight mass spectroscopy (GC-TOF/MS) of the complete murine macrophage ANA-1 cell metabolome was implemented in this study. Using optimized chromatography and mass spectrometry parameters, the metabolites detected by GC-TOF/MS were identified and processed using multivariate statistical analysis, including principal component analysis (PCA) and orthogonal projection on latent-structures discriminant analysis (OPLS-DA). The metabolite sets were screened for further pathway analysis under rules of t-test (P) value < 0.05, VIP value > 1, and similarity value > 500. The mainly interfered metabolism pathways were categorized into two dominant types: amino acid metabolism and glycometabolism. Four metabolites, palmitic acid, 1-monopalmitin, ribose-5-phosphate and 2-deoxy-D-galactose, occur only under combined "DON + ZEN" treatment, indicating abnormal metabolism in ANA-1 cells. The metabolic state of ANA-1 cells under induction by combined "DON + ZEN" illustrates that DON may inhibit the estrogenic effects of ZEN. Thus, the combined effect of "DON + ZEN" may exacerbate toxicity in the pentose phosphate pathway, while palmitic acid metabolism is likely a new pathway effected by the combination, "DON + ZEN."
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science, School of Food Science Synergetic Innovation Center of Food Safety and Nutrition, Jiangnan University, Wuxi, Jiangsu 214122, China. Electronic address: jijianjndx@126.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Dairy Biotechnology, Dairy Research Institute, Bright Dairy & Food Co., Ltd., Shanghai 200436, PR China.
authors.forename: Pei
authors.initials: P
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science, School of Food Science Synergetic Innovation Center of Food Safety and Nutrition, Jiangnan University, Wuxi, Jiangsu 214122, China.
authors.forename: Fuwei
authors.initials: F
authors.lastname: Pi
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science, School of Food Science Synergetic Innovation Center of Food Safety and Nutrition, Jiangnan University, Wuxi, Jiangsu 214122, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science, School of Food Science Synergetic Innovation Center of Food Safety and Nutrition, Jiangnan University, Wuxi, Jiangsu 214122, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science, School of Food Science Synergetic Innovation Center of Food Safety and Nutrition, Jiangnan University, Wuxi, Jiangsu 214122, China.
authors.forename: Jiadi
authors.initials: J
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science, School of Food Science Synergetic Innovation Center of Food Safety and Nutrition, Jiangnan University, Wuxi, Jiangsu 214122, China.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science, School of Food Science Synergetic Innovation Center of Food Safety and Nutrition, Jiangnan University, Wuxi, Jiangsu 214122, China.
authors.forename: Yinzhi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Food Science and Technology, School of Food Science, School of Food Science Synergetic Innovation Center of Food Safety and Nutrition, Jiangnan University, Wuxi, Jiangsu 214122, China. Electronic address: sxlzzz@jiangnan.edu.cn.
authors.forename: Xiulan
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D002460:Cell Line; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D008264:Macrophages / Q000187:drug effects*; D055432:Metabolomics; D051379:Mice; D014255:Trichothecenes / Q000008:administration & dosage / Q000633:toxicity*; D015025:Zearalenone / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D014255:Trichothecenes; D015025:Zearalenone; C007262:deoxynivalenol
keywords: Combined toxicity; Deoxynivalenol; GC-TOF/MS; Metabolomics; Zearalenone