Toxicity and metabolic effect of combined deoxynivalenol,3-acetyldeoxy-nivalenol,and 15-acetyldeoxynivalenol on a Caco-2 cell model  

作　　者：Yongli Ye Kaimin Wei Jian Ji Xiao Ning Jia-Sheng Wang Xiulan Sun 

机构地区：[1]State Key Laboratory of Food Science and Technology,School of Food Science and Technology,National Engineering Research Center for Functional Food,Synergetic Innovation Center of Food Safety and Quality Control,Jiangnan University,Wuxi,Jiangsu,214122,PR China [2]Yixing Institute of Food and Biotechnology Co.,Ltd,Yixing,214200,PR China [3]Department of Environmental Health Science,College of Public Health,University of Georgia,Athens,GA,30602,USA [4]Key Laboratory of Food Quality and Safety for State Market Regulation,National Institute of Food and Drug Control,Beijing,100050,PR China

出　　处：《Food Bioscience》2023年第3期2224-2233,共10页食品生物科学（英文）

基　　金：supported by the National Natural Science Foundation of China(32125031);the National Corn Industry Technol-ogy System(CARS-02-40);the Fundamental Research Funds for the Central Universities(JUSRP222001);the Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province,Jiangnan University.

摘　　要：Deoxynivalenol(DON),3-acetyldeoxynivalenol(3-acetylDON),and 15-acetyldeoxynivalenol(15-acetylDON)are typical type-B trichothecenes produced by Fusarium commonly found in cereals worldwide.Details on the combined toxicity of these mycotoxins remain insufficient.In this study,human colorectal adenocarcinoma Caco-2 cell line was used to analyze the individual and combined toxic effects,together with the potential cytotoxic mechanism,of DON,3-acetylDON,and 15-acetylDON.DON exerted the highest inhibitory rate of cell viability,followed by 15-acetylDON and 3-acetylDON.The binary and ternary combinations exerted an antag-onistic effect on Caco-2 cells at IC50-IC90 treatment doses;meanwhile,3-acetylDON+15-acetylDON at low doses exhibited additive effects,and DON+15-acetylDON and DON+3-acetylDON+15-acetylDON showed synergistic effects.The apoptotic rate and reactive oxygen species level of DON+3-acetylDON were lower than those of DON alone.When Caco-2 cells were treated with trichothecenes individually or in combination,Bcl-2 was significantly down-regulated,and Bax,p53,and caspases genes were up-regulated.Moreover,DON and its acetylated derivatives disrupted amino acid metabolism and protein synthesis.These results indicate that the toxicological effects of trichothecene combinations varied depending on the type of combination and concen-tration.The co-exposure of DON and its derivatives may induce apoptosis of Caco-2 cells by inhibiting protein synthesis,inducing oxidative stress,and regulating the level of apoptosis-related genes.These findings can provide new vision for proposing intervention strategies for co-exposure toxicity of DON and its acetylated derivatives.

关 键 词：DEOXYNIVALENOL TRICHOTHECENE Combined toxicity METABONOMICS 

分 类 号：TS201[轻工技术与工程—食品科学]