| Abstrakt: |
Chiral pollutants often pose significant differential environmental health risks. In this study, the biotransformation of chiral dinotefuran (DIN) and its enantioselective metabolic toxicity mechanisms have been systemically investigated. Firstly, reversed-phase 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 (Ke) 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 revealed. The 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 S-configuration. Meanwhile, 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 dopamine. Thirdly, 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. [ABSTRACT FROM AUTHOR] |
Full text from SpringerLink