Four cypermethrin isomers induced stereoselective metabolism in H295R cells

Abstract

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.

Exploring Release, Isomerization, and Absorption of Cypermethrin in Pacific Oysters (Crassostrea gigas) with Different Processing Methods during In Vivo Digestion: Insights from a Gastrointestinal Tract Quantitative Tracing Method

“…Studies have shown that cis-isomers of CP exhibit a higher metabolic disruption than the trans-isomers, including disruption of glucose and amino acid metabolism, potentially contributing to metabolic syndrome. 7 Additionally, the cis-isomers possess stronger reproductive toxicity, potentially leading to diminished sperm motility. 37 Therefore, in the risk assessment and toxicological studies of CP exposure from consuming oysters, it is important to consider the difference in absorption rates between cis-and trans-isomers.…”

“…In dietary exposure through CP-containing oysters, the cis -isomers of CP might finally accumulate in the body at a higher ratio and further produce toxic effects. Studies have shown that cis -isomers of CP exhibit a higher metabolic disruption than the trans -isomers, including disruption of glucose and amino acid metabolism, potentially contributing to metabolic syndrome . Additionally, the cis -isomers possess stronger reproductive toxicity, potentially leading to diminished sperm motility .…”

“…The CP isomers exhibit variations in insecticidal activity, environmental behavior, metabolic processes, and toxicity. , Therefore, the toxicity of different CP subsets varies according to the types and proportions of CP isomers. The α-CP displayed a stronger endocrine and hepato-renal toxicity, while β-CP exhibited a greater reproductive and immunotoxicity. − In this study, β-CP was selected as the contaminant for oysters due to its widespread commercial availability as an insecticide and its significant contribution to CP contamination in both environmental and food contexts.…”