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.

中文翻译：

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四种氯氰菊酯异构体可诱导H295R细胞中的立体选择性代谢。

氯氰菊酯（CP）被广泛用于控制农业和室内害虫。先前的研究报道了CP在生物活性方面的立体选择性差异。然而，关于它们在代谢表型和内分泌干扰作用之间的潜在机制知之甚少。本文中，基于核磁共振（NMR）的代谢组学结合了代谢物鉴定和途径分析，用于评估人肾上腺皮质癌细胞（H295R）培养基中CP异构体诱导的立体选择性代谢异常。然后，评估与代谢途径受损有关的基因表达水平，以根据代谢表型进行验证。代谢组学研究表明，[（S）-氰基（3-苯氧基苯基）甲基]（1 R，3 R基）-3-（2,2-二氯基）-2,2-二甲基环-1-甲酸叔丁酯[（1 - [R，3 - [R，α小号）- CP诱导的代谢表型比没有其它立体异构体的最显著变化。有10种差异代谢物（异亮氨酸，缬氨酸，亮氨酸，乙醇，丙氨酸，乙酸盐，天冬氨酸，精氨酸，乳酸盐和葡萄糖）以及两种明显受干扰的途径，包括“丙酮酸代谢”和“丙氨酸，天冬氨酸和谷氨酸代谢， ”在细胞H295R培养基中确认（1 - [R，3 - [R，α小号）-CP与其他立体异构体相比。聚合酶链反应（PCR）阵列也证实了代谢组学的结果。我们的结果有助于理解代谢表型中的异构体选择性与内分泌干扰作用之间的潜在机制。此处提供的数据不仅使科学家和研究人员发出的警告具有真实性，而且为环境与政治法规之间的平衡提供了解决方案。