As the number of reported deoxynivalenol (DON) contamination incidents increased steadily over the past decades, there has been a widespread interest in understanding the cellular mechanisms of the toxicological effects of DON usingin vitro systems and omics technologies. The present investigation was conducted to understand the metabolomic changes in human hepatocellular carcinoma cells (HepG2) exposed to 10 μM DON for short term (4 h) and long term (12 h) periods, using a non-targeted metabolomics approach. Our results revealed a remarkable metabolic shift from short term to long term exposure to DON in HepG2 cells. Our metabolomics data also confirmed the role of DON induced oxidative stress in DON toxicity. Coupled with pattern recognition and pathway analysis, effects of DON on redox homeostasis, energy balance, lipid metabolism, and potential toxicological mechanisms were discussed, which would facilitate further studies on the risk assessment of the dietary mycotoxin DON.
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Bai, J., Wang, M.X., Chowbay, B., Ching, C.B. and Chen, W.N., 2011. Metabolic profiling of HepG2 cells incubated with S(-) and R(+) enantiomers of anti-coagulating drug warfarin. Metabolomics 7: 353-362.
'Metabolic profiling of HepG2 cells incubated with S(-) and R(+) enantiomers of anti-coagulating drug warfarin ' () 7 Metabolomics : 353 -362.
Beger, R.D., Sun, J. and Schnackenberg, L.K., 2010. Metabolomics approaches for discovering biomarkers of drug-induced hepatotoxicity and nephrotoxicity. Toxicology and Applied Pharmacology 243: 154-166.
'Metabolomics approaches for discovering biomarkers of drug-induced hepatotoxicity and nephrotoxicity ' () 243 Toxicology and Applied Pharmacology : 154 -166.
Benjamini, Y. and Yekutieli, D., 2001. The control of the false discovery rate in multiple testing under dependency. Annals of Statistics 29: 1165-1188.
'The control of the false discovery rate in multiple testing under dependency ' () 29 Annals of Statistics : 1165 -1188.
Bensassi, F., El Golli-Bennour, E., Abid-Essefi, S., Bouaziz, C., Hajlaoui, M.R. and Bacha, H., 2009. Pathway of deoxynivalenol-induced apoptosis in human colon carcinoma cells. Toxicology 264: 104-109.
'Pathway of deoxynivalenol-induced apoptosis in human colon carcinoma cells ' () 264 Toxicology : 104 -109.
Berg, J.M., Tymoczko, J.L. and Stryer, L., 2002. Biochemistry, 5th edition. W.H. Freeman and Co., New York, NY, USA.
'Biochemistry, 5th edition ', (W.H. Freeman and Co. , New York, NY, USA ).
Coen, M., Holmes, E., Lindon, J.C. and Nicholson, J.K., 2008. NMR-based metabolic profiling and metabonomic approaches to problems in molecular toxicology. Chemical Research in Toxicology 21: 9-27.
'NMR-based metabolic profiling and metabonomic approaches to problems in molecular toxicology ' () 21 Chemical Research in Toxicology : 9 -27.
Cortinovis, C., Pizzo, F., Spicer, L.J. and Caloni, F., 2013.Fusarium mycotoxins: effects on reproductive function in domestic animals – a review. Theriogenology 80: 557-564.
'Fusarium mycotoxins: effects on reproductive function in domestic animals – a review ' () 80 Theriogenology : 557 -564.
Dayoub, R., Thasler, W.E., Bosserhoff, A.K., Singer, T., Jauch, K.W., Schlitt, H.J. and Weiss, T.S., 2006. Regulation of polyamine synthesis in human hepatocytes by hepatotrophic factor augmenter of liver regeneration. Biochemical and Biophysical Research Communications 345: 181-187.
'Regulation of polyamine synthesis in human hepatocytes by hepatotrophic factor augmenter of liver regeneration ' () 345 Biochemical and Biophysical Research Communications : 181 -187.
European Commission (EC), 2006. Commission regulation No. 401/2006 laying down the methods of sampling and analysis for the official control of the levels of mycotoxins in foodstuffs. Official Journal of the European Union L70: 12-34.
Evans, A.M., DeHaven, C.D., Barrett, T., Mitchell, M. and Milgram, E., 2009. Integrated, nontargeted ultrahigh performance liquid chromatography/electrospray ionization tandem mass spectrometry platform for the identification and relative quantification of the small-molecule complement of biological systems. Analytical Chemistry 81: 6656-6667.
'Integrated, nontargeted ultrahigh performance liquid chromatography/electrospray ionization tandem mass spectrometry platform for the identification and relative quantification of the small-molecule complement of biological systems ' () 81 Analytical Chemistry : 6656 -6667.
Garrett, R.H. and Grisham, C.M., 2012. Biochemistry, 5th edition. Cengage Learning Inc., Boston, MA, USA.
'Biochemistry, 5th edition ', (Cengage Learning Inc. , Boston, MA, USA ).
Ghesquière, B., Wong, B.W., Kuchnio, A. and Carmeliet, P., 2014. Metabolism of stromal and immune cells in health and disease. Nature 511: 167-176.
'Metabolism of stromal and immune cells in health and disease ' () 511 Nature : 167 -176.
Hopton, R.P., Turner, E., Burley, V.J., Turner, P.C. and Fisher, J., 2010. Urine metabolite analysis as a function of deoxynivalenol exposure: an NMR-based metabolomics investigation. Food Additives and Contaminants Part A 27: 255-261.
'Urine metabolite analysis as a function of deoxynivalenol exposure: an NMR-based metabolomics investigation ' () 27 Food Additives and Contaminants Part A : 255 -261.
Hu, C., Shi, J., Quan, S., Cui, B., Kleessen, S., Nikoloski, Z. and Zhang, D., 2014. Metabolic variation between japonica and indica rice cultivars as revealed by non-targeted metabolomics. Scientific Reports 4: 5067-5077.
'Metabolic variation between japonica and indica rice cultivars as revealed by non-targeted metabolomics ' () 4 Scientific Reports : 5067 -5077.
Königs, M., Schwerdt, G., Gekle, M. and Humpf, H.U., 2008. Effects of the mycotoxin deoxynivalenol on human primary hepatocytes. Molecular Nutrition and Food Research 52: 830-839.
'Effects of the mycotoxin deoxynivalenol on human primary hepatocytes ' () 52 Molecular Nutrition and Food Research : 830 -839.
Königs, M., Lenczyk, M., Schwerdt, G., Holzinger, H., Gekle, M. and Humpf, H.U., 2007. Cytotoxicity, metabolism and cellular uptake of the mycotoxin deoxynivalenol in human proximal tubule cells and lung fibroblasts in primary culture. Toxicology 240: 48-59.
'Cytotoxicity, metabolism and cellular uptake of the mycotoxin deoxynivalenol in human proximal tubule cells and lung fibroblasts in primary culture ' () 240 Toxicology : 48 -59.
Kotera, M., Hirakawa, M., Tokimatsu, T., Goto, S. and Kanehisa, M., 2012. The KEGG databases and tools facilitating omics analysis: latest developments involving human diseases and pharmaceuticals. Methods in Molecular Biology 802: 19-39.
'The KEGG databases and tools facilitating omics analysis: latest developments involving human diseases and pharmaceuticals ' () 802 Methods in Molecular Biology : 19 -39.
Li, D., Ye, Y., Lin, S., Deng, L., Fan, X., Zhang, Y. and Ma, Y., 2014. Evaluation of deoxynivalenol-induced toxic effects on DF-1 cellsin vitro: cell-cycle arrest, oxidative stress, and apoptosis. Environmental Toxicology and Pharmacology 37: 141-149.
'Evaluation of deoxynivalenol-induced toxic effects on DF-1 cellsin vitro: cell-cycle arrest, oxidative stress, and apoptosis ' () 37 Environmental Toxicology and Pharmacology : 141 -149.
Massimi, M., Tomassini, A., Sciubba, F., Sobolev, A.P., Devirgiliis, L.C. and Miccheli, A., 2012. Effects of resveratrol on HepG2 cells as revealed by 1H-NMR based metabolic profiling. Biochimica et Biophysica Acta – General Subjects 1820: 1-8.
'Effects of resveratrol on HepG2 cells as revealed by 1H-NMR based metabolic profiling ' () 1820 Biochimica et Biophysica Acta – General Subjects : 1 -8.
Mishra, S., Dwivedi, P.D., Pandey, H.P. and Das, M., 2014. Role of oxidative stress in Deoxynivalenol induced toxicity. Food and Chemical Toxicology 72: 20-29.
'Role of oxidative stress in Deoxynivalenol induced toxicity ' () 72 Food and Chemical Toxicology : 20 -29.
Nielsen, C., Lippke, H., Didier, A., Dietrich, R. and Märtlbauer, E., 2009. Potential of deoxynivalenol to induce transcription factors in human hepatoma cells. Molecular Nutrition and Food Research 53: 479-491.
'Potential of deoxynivalenol to induce transcription factors in human hepatoma cells ' () 53 Molecular Nutrition and Food Research : 479 -491.
Ohta, T., Masutomi, N., Tsutsui, N., Sakairi, T., Mitchell, M., Milburn, M.V. and Guo, L., 2009. Untargeted metabolomic profiling as an evaluative tool of fenofibrate-induced toxicology in Fischer 344 male rats. Toxicologic Pathology 37: 521-535.
'Untargeted metabolomic profiling as an evaluative tool of fenofibrate-induced toxicology in Fischer 344 male rats ' () 37 Toxicologic Pathology : 521 -535.
Pestka, J.J. and Smolinski, A.T., 2005. Deoxynivalenol: toxicology and potential effects on humans. Journal of Toxicology and Environmental Health, Part B 8: 39-69.
'Deoxynivalenol: toxicology and potential effects on humans ' () 8 Journal of Toxicology and Environmental Health, Part B : 39 -69.
Pestka, J.J., Zhou, H.R., Moon, Y. and Chung, Y.J., 2004. Cellular and molecular mechanisms for immune modulation by deoxynivalenol and other trichothecenes: unraveling a paradox. Toxicology Letters 153: 61-73.
'Cellular and molecular mechanisms for immune modulation by deoxynivalenol and other trichothecenes: unraveling a paradox ' () 153 Toxicology Letters : 61 -73.
Pestka, J. and Zhou, H.R., 2006. Toll-like receptor priming sensitizes macrophages to proinflammatory cytokine gene induction by deoxynivalenol and other toxicants. Toxicological Sciences 92: 445-455.
'Toll-like receptor priming sensitizes macrophages to proinflammatory cytokine gene induction by deoxynivalenol and other toxicants ' () 92 Toxicological Sciences : 445 -455.
Pestka, J.J., 2010. Deoxynivalenol: mechanisms of action, human exposure, and toxicological relevance. Archives of Toxicology 84: 663-679.
'Deoxynivalenol: mechanisms of action, human exposure, and toxicological relevance ' () 84 Archives of Toxicology : 663 -679.
Pestka, J.J., 2008. Mechanisms of deoxynivalenol-induced gene expression and apoptosis. Food Additives and Contaminants Part A 25: 1128-1140.
'Mechanisms of deoxynivalenol-induced gene expression and apoptosis ' () 25 Food Additives and Contaminants Part A : 1128 -1140.
Pike, L.S., Smift, A.L., Croteau, N.J., Ferrick, D.A. and Wu, M., 2011. Inhibition of fatty acid oxidation by etomoxir impairs NADPH production and increases reactive oxygen species resulting in ATP depletion and cell death in human glioblastoma cells. Biochimica et Biophysica Acta – Bioenergetics 1807: 726-734.
'Inhibition of fatty acid oxidation by etomoxir impairs NADPH production and increases reactive oxygen species resulting in ATP depletion and cell death in human glioblastoma cells ' () 1807 Biochimica et Biophysica Acta – Bioenergetics : 726 -734.
Ran, R., 2014. The safety assessment of deoxynivalenol and specificity determination of genetically modified rice Kefeng 6. MSc-Dissertation, Shanghai Jiao Tong University, Shanghai, China P.R.
Ran, R., Wang, C., Han, Z., Wu, A., Zhang, D. and Shi, J., 2013a. Determination of deoxynivalenol (DON) and its derivatives: current status of analytical methods. Food Control 34: 138-148.
'Determination of deoxynivalenol (DON) and its derivatives: current status of analytical methods ' () 34 Food Control : 138 -148.
Ran, R., Zhang, W., Cui, B., Xu, Y., Han, Z., Wu, A. and Shi, J., 2013b. A simple and rapid method for the determination of deoxynivalenol in human cells by UPLC-TOF-MS. Analytical Methods 5: 5637-5643.
'A simple and rapid method for the determination of deoxynivalenol in human cells by UPLC-TOF-MS ' () 5 Analytical Methods : 5637 -5643.
Rao, J., Cheng, F., Hu, C., Quan, S., Lin, H., Wang, J. and Shi, J., 2014. Metabolic map of mature maize kernels. Metabolomics 10: 775-787.
'Metabolic map of mature maize kernels ' () 10 Metabolomics : 775 -787.
Rizzo, A.F., Atroshi, F., Ahotupa, M., Sankari, S. and Elovaara, E., 1994. Protective effect of antioxidants against free radical-mediated lipid peroxidation induced by DON or T-2 toxin. Journal of Veterinary Medicine Series A 41: 81-90.
'Protective effect of antioxidants against free radical-mediated lipid peroxidation induced by DON or T-2 toxin ' () 41 Journal of Veterinary Medicine Series A : 81 -90.
Rocha, O., Ansari, K. and Doohan, F.M., 2005. Effects of trichothecene mycotoxins on eukaryotic cells: a review. Food Additives and Contaminants 22: 369-378.
'Effects of trichothecene mycotoxins on eukaryotic cells: a review ' () 22 Food Additives and Contaminants : 369 -378.
Romero, R., Mazaki-Tovi, S., Vaisbuch, E., Kusanovic, J.P., Chaiworapongsa, T., Gomez, R. and Beecher, C., 2010. Metabolomics in premature labor: a novel approach to identify patients at risk for preterm delivery. Journal of Maternal-Fetal and Neonatal Medicine 23: 1344-1359.
'Metabolomics in premature labor: a novel approach to identify patients at risk for preterm delivery ' () 23 Journal of Maternal-Fetal and Neonatal Medicine : 1344 -1359.
Ruiz-Aracama, A., Peijnenburg, A., Kleinjans, J., Jennen, D., Van Delft, J., Hellfrisch, C. and Lommen, A., 2011. An untargeted multi-technique metabolomics approach to studying intracellular metabolites of HepG2 cells exposed to 2,3,7,8-tetrachlorodibenzop-dioxin. BMC Genomics 12: 251.
'An untargeted multi-technique metabolomics approach to studying intracellular metabolites of HepG2 cells exposed to 2,3,7,8-tetrachlorodibenzop-dioxin ' () 12 BMC Genomics : 251.
Shen, Z., Wu, W. and Hazen, S.L., 2000. Activated leukocytes oxidatively damage DNA, RNA, and the nucleotide pool through halide-dependent formation of hydroxyl radical. Biochemistry 39: 5474-5482.
'Activated leukocytes oxidatively damage DNA, RNA, and the nucleotide pool through halide-dependent formation of hydroxyl radical ' () 39 Biochemistry : 5474 -5482.
Sobrova, P., Adam, V., Vasatkova, A., Beklova, M., Zeman, L. and Kizek, R., 2010. Deoxynivalenol and its toxicity. Interdisciplinary Toxicology 3: 94-99.
'Deoxynivalenol and its toxicity ' () 3 Interdisciplinary Toxicology : 94 -99.
Valluru, R. and Van den Ende, W., 2011. Myo-inositol and beyond – Emerging networks under stress. Plant Science 181: 387-400.
'Myo-inositol and beyond – Emerging networks under stress ' () 181 Plant Science : 387 -400.
Van Vliet, E., Morath, S., Eskes, C., Linge, J., Rappsilber, J., Honegger, P. and Coecke, S., 2008. A novelin vitro metabolomics approach for neurotoxicity testing, proof of principle for methyl mercury chloride and caffeine. Neurotoxicology 29: 1-12.
'A novelin vitro metabolomics approach for neurotoxicity testing, proof of principle for methyl mercury chloride and caffeine ' () 29 Neurotoxicology : 1 -12.
Waché, Y.J., Hbabi-Haddioui, L., Guzylack-Piriou, L., Belkhelfa, H., Roques, C. and Oswald, I.P., 2009. The mycotoxin deoxynivalenol inhibits the cell surface expression of activation markers in human macrophages. Toxicology 262: 239-244.
'The mycotoxin deoxynivalenol inhibits the cell surface expression of activation markers in human macrophages ' () 262 Toxicology : 239 -244.
Warth, B., Sulyok, M. and Krska, R., 2013. LC-MS/MS-based multibiomarker approaches for the assessment of human exposure to mycotoxins. Analytical and Bioanalytical Chemistry 405: 5687-5695.
'LC-MS/MS-based multibiomarker approaches for the assessment of human exposure to mycotoxins ' () 405 Analytical and Bioanalytical Chemistry : 5687 -5695.
Winkler, J., Sotiriadou, I., Chen, S., Hescheler, J. and Sachinidis, A., 2009. The potential of embryonic stem cells combined with-omics technologies as model systems for toxicology. Current Medicinal Chemistry 16: 4814-4827.
'The potential of embryonic stem cells combined with-omics technologies as model systems for toxicology ' () 16 Current Medicinal Chemistry : 4814 -4827.
Wishart, D.S., Jewison, T., Guo, A.C., Wilson, M., Knox, C., Liu, Y. and Scalbert, A., 2013. HMDB 3.0 – the human metabolome database in 2013. Nucleic Acids Research 41: 801-807.
'HMDB 3.0 – the human metabolome database in 2013 ' () 41 Nucleic Acids Research : 801 -807.
Zhang, X., Jiang, L., Geng, C., Cao, J. and Zhong, L., 2009. The role of oxidative stress in deoxynivalenol-induced DNA damage in HepG2 cells. Toxicon 54: 513-518.
'The role of oxidative stress in deoxynivalenol-induced DNA damage in HepG2 cells ' () 54 Toxicon : 513 -518.
| All Time | Past 365 days | Past 30 Days | |
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As the number of reported deoxynivalenol (DON) contamination incidents increased steadily over the past decades, there has been a widespread interest in understanding the cellular mechanisms of the toxicological effects of DON usingin vitro systems and omics technologies. The present investigation was conducted to understand the metabolomic changes in human hepatocellular carcinoma cells (HepG2) exposed to 10 μM DON for short term (4 h) and long term (12 h) periods, using a non-targeted metabolomics approach. Our results revealed a remarkable metabolic shift from short term to long term exposure to DON in HepG2 cells. Our metabolomics data also confirmed the role of DON induced oxidative stress in DON toxicity. Coupled with pattern recognition and pathway analysis, effects of DON on redox homeostasis, energy balance, lipid metabolism, and potential toxicological mechanisms were discussed, which would facilitate further studies on the risk assessment of the dietary mycotoxin DON.
| All Time | Past 365 days | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 459 | 128 | 21 |
| Full Text Views | 29 | 2 | 0 |
| PDF Views & Downloads | 5 | 0 | 0 |