The Metabolic Responses Of Human HepG2 Cells To The Exposure Of Deoxynivalenol And Elaidic Acid

Along with people living standard enhancement,food safety has become one of the most focused issues.In China,There are increasing reports about the food contamination with deoxynivalenol,a fungi produced mycotoxin,and the presence of dietary elaidic acids in many foods.To assist the risk assessment of deoxynivalenol and elaidic acid,and to improve people's awareness of the detrimental effects of these food derived substances,we carried out in vitro analysis to evaluate the metabolic response of HepG2 cells to the exposure of deoxynivalenol and elaidic acid in this study.1.The metabolic response of human HepG2 cells to the exposure of deoxynivalenol.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 using in vitro systems and omics technologies.The present investigation was conducted to determine the toxicological mechanisms in human hepatocellular carcinoma cells(HepG2)exposed to 10 ?M DON for 4 h(short term)and 12 h(long term)period using a nontargeted metabolomics approach.We revealed a remarkable metabolic shift from short term to long term exposure to DON in HepG2 cells.Short term DON treatment mainly changed metabolism of nucleotides,cofactors,and vitamins,while long term DON treatment altered mainly the metabolism of lipids.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 hemostasis,energy balance,lipid metabolism,and potential toxicological mechanisms were discussed,which would facilitate further studies on the risk assessment of the dietary mycotoxin DON.2.The metabolomic changes of human HepG2 cells to the exposure of elaidic acid.Trans-fatty acids are often found in our daily diets.Recently,increasing evidence from both toxicological and exposure assessment studies shows that trans-fatty acids are detrimental to human healthy,therefore,the dietary intake of trans-fatty acids is becoming an issue of food safety.In this study,the human cell line HepG2 was used as a model to understand the metabolomic responses of human cells to the exposure of elaidic acid,with the aim to reveal the molecular mechanisms underlying its harmful effects on human health.Based on the preliminary result of toxicological assay,HepG2 cells were treated with 1.2 mM and 1.5 mM elaidic acid for 6 and 12 h,respectively,and the metabolomes of these cells were analyzed using a non-targeted platform composing of UPLC-MS/MS and GC-MS.Statistic data revealed that treatment with elaidic acid resulted in remarkable changes in HepG2 cells at the metabolomic level,particularly changes in lipid metabolism,cholesterol metabolism and carbon-nitrogen metabolism,which is treatment time dependent.Those in vitro metabolomic data provided novel insights into the detrimental effects of trans-fatty acids on human health.