Stereoselective toxicity mechanism of neonicotinoid dinotefuran in honeybees: New perspective from a spatial metabolomics study

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 by S-(+)-dinotefuran than R-(-)-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 acidmetabolisms within honeybees. Taken together, the integrated MSI and metabolomics results indicated the higher toxicity of S-(+)-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. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

In this study, an integrated mass spectrometry imaging (MSI) and untargeted metabolomics method was used to investigate the metabolic regulation of honeybees in response to stereoisomeric dinotefuran pesticides. The results indicated that S-(+)-dinotefuran had higher toxicity than R-(-)-dinotefuran, affecting multiple metabolic pathways and energy metabolism in honeybees. The findings provide new perspectives for the development and applications of pure chiral agrochemicals.