Journal
TOXICON
Volume 120, Issue -, Pages 175-184Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.toxicon.2016.08.003
Keywords
Deoxynivalenol; Zearalenone; Combined toxicity; Metabolomics; GC-TOF/MS
Categories
Funding
- National Science & Technology Pillar Program during the Five-Year Plan Period [2012BAD12B08]
- Science and Technology Commission of Shanghai Municipality [16DZ2280600]
- Special Fund for Food in the Public Interest [201513006]
- National Research Program [31371768]
- Program for New Century Excellent Talents in Jiangnan University [NCET-12-0877]
- Qinglan Project
- Industry Development Program in Industry Innovation Center for Food safety and quality control of Jiangsu province [1026010241140870-39]
- Priority Academic Program Development of Jiangsu Higher Education Institutions
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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. (C) 2016 Elsevier Ltd. All rights reserved.
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