Stereoselective toxicity mechanism of neonicotinoid dinotefuran in honeybees: New perspective from a spatial metabolomics study
Stereoselective toxicity mechanism of neonicotinoid dinotefuran in honeybees: New perspective from a spatial metabolomics study
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新烟碱类呋虫胺对蜜蜂的立体选择性毒性机制：空间代谢组学研究的新视角
DOI：
10.1016/j.scitotenv.2021.151116
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发表时间：
2022
影响因子：
9.8
通讯作者：
Wu Xinzhou
中科院分区：
文献类型：
--
作者：
Zhang Yue;Chen Dong;Xu Yizhu;Ma Lianlian;Du Mingyi;Li Ping;Yin Zhibin;Xu Hanhong;Wu Xinzhou
开发低毒性的立体异构体新烟碱类农药是防止全球蜜蜂种群减少的关键，但目前对蜜蜂对立体异构体农药的原位代谢调节知之甚少。在此，我们展示了一种集成质谱成像（MSI）和非靶向代谢组学方法，以揭示与立体异构体呋喃相关的蜜蜂（Apis cerana）紊乱的代谢表达水平和空间分化。这种方法提供了代谢网络映射能力，涉及蜜蜂多种代谢途径的广泛代谢物。代谢组学结果表明，与r -(−)-dinotefuran相比，ys -(+)-dinotefuran可以显著影响蜜蜂更多的代谢途径，如三羧酸（TCA）循环、乙醛酸盐和二羧酸盐代谢以及各种氨基酸代谢。MSI结果表明，蜜蜂体内涉及TCA循环、嘌呤、糖酵解和氨基酸代谢的关键代谢物存在交叉调节和空间分化。综上所述，综合MSI和代谢组学结果表明，s -(+)-呋喃的高毒性源于代谢途径紊乱及其对能量代谢的抑制作用，导致解毒机制的降解率显著降低。从空间代谢组学的角度来看，我们的研究结果为纯手性农药的开发和应用提供了新的视角。
Development of stereoisomeric neonicotinoid pesticides with lower toxicity is key to preventing global population declines of honeybees, whereas little is known about the in situ metabolic regulation of honeybees in response to stereoisomeric pesticides. Herein, we demonstrate an integrated mass spectrometry imaging (MSI) and untargeted metabolomics method to disclose disturbed metabolic expression levels and spatial differentiation in honeybees (Apis cerana) associated with stereoisomeric dinotefuran. This method affords a metabolic network mapping capability regarding a wide range of metabolites involved in multiple metabolic pathways in honeybees. Metabolomics results indicate more metabolic pathways of honeybees can be significantly affected byS-(+)-dinotefuran thanR-(−)-dinotefuran, such as tricarboxylic acid (TCA) cycle, glyoxylate and dicarboxylate metabolism, and various amino acid metabolisms. MSI results demonstrate the cross-regulation and spatial differentiation of crucial metabolites involved in the TCA cycle, purine, glycolysis, and amino acid metabolisms within honeybees. Taken together, the integrated MSI and metabolomics results indicated the higher toxicity ofS-(+)-dinotefuran arises from metabolic pathway disturbance and its inhibitory role in the energy metabolism, resulting in significantly reduced degradation rates of detoxification mechanisms. From the view of spatial metabolomics, our findings provide novel perspectives for the development and applications of pure chiral agrochemicals.