The stereoselective metabolic disruption of cypermethrin on rats by a sub-acute study based on metabolomics

Due to the massive application of cypermethrin (CYP) for pest control in China, the adverse effects on non-target organisms have aroused great attention. However, comparative studies between its different stereoisomers remain scarce, especially for metabolism perturbations. Herein, the rats were administered α-CYP, β-CYP, and θ-CYP by gavage at doses of 8.5, 29.2, and 25.0 mg/kg/day, respectively, for 28 consecutive days. By blood examination, significant changes in liver and renal function parameters were observed in rats exposed to all three CYPs. The stereoisomeric selectivity in metabolic disturbances was assessed based on a metabolomic strategy via multivariate analysis and pathway analysis. The results demonstrated that amino acid and glycolipid metabolism were disrupted in all CYP groups. Among them, the most significant changes in the metabolic phenotype were observed in the θ-CYP group, with 56 differential metabolites enriched in 9 differential metabolic pathways. At the same time, the endogenous metabolite trimethylamine oxide (TMAO), which is closely linked to the gut microbiota, was also significantly elevated in this group. Gender differences were found in α- and θ-CYP-exposed rats, with perturbations in amino acid and glucose metabolism of greater concern in females and lipid metabolism of greater concern in males. Overall, β-CYP exhibited a lower risk of metabolic perturbations than α-CYP or θ-CYP, which helps to screen suitable agrochemical products for green agricultural development.