Aldehyde oxidase mediated enantioselective metabolic health risk of dinotefuran

作     者：Liwei Xu Xinxin Xu Hua Kuang Chuanlai Xu Xiaoling Wu 

作者机构：State Key Laboratory of Food Science and ResourcesJiangnan UniversityWuxi214122China International Joint Research Laboratory for Biointerface and Biodetection and School of Food Science and TechnologyJiangnan UniversityWuxi214122China Collaborative Innovation center of Food Safety and Quality Control in Jiangsu ProvinceJiangnan UniversityWuxi214122China 

出 版 物：《Science China Chemistry》 (中国科学（化学英文版）)

年 卷 期：2024年第67卷第6期

页      面：2079-2091页

核心收录：

学科分类：081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 09[农学] 0903[农学-农业资源与环境] 070302[理学-分析化学] 0703[理学-化学] 

基　　金：supported by the National Natural Science Foundation of China(22276076,22306074,22361132536,22236002) the Fundamental Research Funds for the Central Universities(JUSRP622032) the Jiangsu Association for Science and Technology Youth Science and Technology Talent Support Project(TJ2021-049) 

主　　题：neonicotinoid dinotefuran enantiomer aldehyde oxidase metabolomics health risk 

摘      要：Chiral pollutants often pose significant differential environmental health *** this study,the biotransformation of chiral dinotefuran(DIN)and its enantioselective metabolic toxicity mechanisms have been systemically ***,reversedphase chromatography-high resolution mass spectrometry was developed to quantify the content of DIN R/S chiral enantiomer with pg level sensitivity,revealing a lower elimination rate constant(K_(e))of S-DIN(0.730 h^(-1))than R-DIN(0.746 h^(-1)).Secondly,the interaction mechanism between DIN metabolism and important endogenous bioactive molecules,such as aldehyde oxidase(AOX)and neurotransmitters,was *** DIN nitro-group was converted into a guanidine group by the reducing site of nearby flavin adenine dinucleotide(FAD)in AOX with the preferred higher affinity of ***,the endogenous tryptophan(Trp)aldehyde metabolic intermediate,5-hydroxyindoleacetaldehyde(5-HIAL),provides a persistent electron donor for DIN reduction via the oxidation-catalyzed site in AOX,resulting in remarkable up-regulation of monoamine neurotransmitters such as serotonin and ***,the higher level of neurotransmitters further mediated dysregulation of oxylipin homeostasis via the serotonergic pathway,where S-DIN exhibited more pronounced liver lipid damage and environmental health risk with the accumulated lipid biomarkers,oxidized triglyceride(OxTG)and oxidized sphingomyelin(OxSM).This study elucidates the AOX-mediated enantioselectivity metabolic pathway of DIN,providing a new analytical method for chiral pollutants and paves the way for their health risk assessments.