Cypermethrin (CP) is widely used for controlling agricultural and indoor vermin. Previous studies have reported the stereoselective difference of CP in biological activities. However, little is known about their potential mechanisms between metabolic phenotypes and endocrine‐disrupting effects. Herein, nuclear magnetic resonance (NMR)‐based metabolomics combining metabolite identification and pathway analysis were applied to evaluate the stereoselective metabolic cdisorders induced by CP isomers in human adrenocortical carcinoma cells (H295R) culture medium. Then, gene expression levels related to disturbed metabolic pathways were assessed to verify according to metabolic phenotypes. Metabolomics profiles showed that [(S)‐cyano(3‐phenoxyphenyl)methyl](1R,3R)‐3‐(2,2‐dichloroethenyl)‐2,2‐dimethylcyclopropane‐1‐carboxylate [(1R,3R,αS)‐CP] induced the most significant changes in metabolic phenotypes than did the other stereoisomers. There are 10 differential metabolites (isoleucine, valine, leucine, ethanol, alanine, acetate, aspartate, arginine, lactate, and glucose) as well as two significantly disturbed pathways, including “pyruvate metabolism” and “alanine, aspartate, and glutamate metabolism,” that were confirmed in H295R cells culture medium of (1R,3R,αS)‐CP compared with other stereoisomers. Polymerase chain reaction (PCR) array also confirmed the results of metabolomics. Our results can help to understand the potential mechanisms between the isomer selectivity in metabolic phenotypes and endocrine‐disrupting effects. Data provided here not only lend authenticity to the cautions issued by the scientists and researchers but also offer a solution for the balance between environment and political regulations.
Over 30% of commercial pesticides are racemic mixtures. Nowadays, the environmental safety of chiral pesticides has received more and more attention. Metalaxyl is a broad-spectrum fungicide with systemic function, which has a chiral carbon. Although its fungicidal activity almost entirely originates from the R-enantiomer, the enantioselective toxicity of metalaxyl in animals and human beings are not yet clear. In this study, the urinary metabolomics approach was applied to analyze the changes in metabolic phenotypes in adolescent rats by using nuclear magnetic resonance (NMR). In the urinary metabolomics results, the metabolic profiles of the different enantiomers were distinguishable, and the characteristic metabolites were different. Both in the exposure of R/S-enantiomers, the disturbed metabolic pathways in common were butanoate metabolism, valine, leucine and isoleucine biosynthesis, alanine, aspartate and glutamate metabolism, and glutamine and glutamate metabolism. These pathways were closely involved in gut microbiota. In addition to the disturbed metabolic pathways common to both, three metabolic pathways were abnormal in the exposure of S-metalaxyl, including aminoacyl-tRNA biosynthesis, arginine biosynthesis, and citrate cycle. These disturbed metabolic pathways could cause genetic diseases and affect the liver function. These results indicate that a specific insight into the effects of different metalaxyl enantiomers on metabolic disturbance. Our work could allow us to well understand the health risk assessments of metalaxyl enantiomers, especially at the metabolic level.
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