Imidacloprid (IMI) is one of the most frequently used neonicotinoid insecticides, but recent studies have shown adverse effects on mammals. IMI was found to be neurotoxic and hepatotoxic. In the present study, the effects of repeated oral administration of two doses of IMI (5 and 20 mg/kg/day) for 28 days on hippocampus and liver of female KM mice were studied. The histopathological and biochemical experiments indicated obvious damages to the hippocampus and liver of mice in the high-dose group (20 mg/kg/day). Using a high-throughput metabolomics platform based on ultrahigh performance liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS), we studied effects of IMI on metabolic profiles in the hippocampus and liver of mice. Significant differences among the control group, the low-dose group and the high-dose group were clearly presented using multivariate analysis. The changed metabolic profile in the low-dose group (5 mg/kg/day) revealed that the metabolic disturbance in the hippocampus and liver of mice had been induced by low-dose of IMI, although no significant histopathological changes were observed in the low-dose group. Six differential metabolites in the hippocampus and 10 differential metabolites in the liver were identified as the possible biomarkers to distinguish IMI exposure from the control group using the variable importance in projection (VIP) value and receiver operating characteristic (ROC) analysis. The metabolism disturbances of important biochemical pathways in the hippocampus and liver of mice in the exposed groups were elucidated, mostly concentrated in lipid metabolism, amino acid metabolism, nucleotide metabolism, carbohydrate metabolism, and energy metabolism (p < 0.05). Such investigations give out a global view of IMI-induced damages in the hippocampus and liver of mice and imply a health risk associated with early metabolic damage in mice.

吡虫啉 (IMI) 是最常用的新烟碱类杀虫剂之一，但最近的研究表明对哺乳动物有不利影响。 IMI被发现具有神经毒性和肝毒性。在本研究中，研究了连续28天重复口服两种剂量的IMI（5和20 mg/kg/天）对雌性KM小鼠海马和肝脏的影响。组织病理学和生化实验表明，高剂量组（20mg/kg/天）小鼠海马和肝脏有明显损伤。使用基于超高效液相色谱/混合四极杆飞行时间质谱 (UPLC/Q-TOF MS) 的高通量代谢组学平台，我们研究了 IMI 对小鼠海马和肝脏代谢谱的影响。使用多变量分析清楚地显示了对照组、低剂量组和高剂量组之间的显着差异。低剂量组（5 mg/kg/天）代谢谱的变化表明，低剂量 IMI 引起了小鼠海马和肝脏的代谢紊乱，尽管低剂量组没有观察到明显的组织病理学变化。 -剂量组。使用投影变量重要性 (VIP) 值和受试者工作特征 (ROC) 分析，将海马中的 6 种差异代谢物和肝脏中的 10 种差异代谢物确定为可能的生物标志物，以区分 IMI 暴露与对照组。阐明了暴露组小鼠海马和肝脏重要生化通路的代谢紊乱，主要集中在脂质代谢、氨基酸代谢、核苷酸代谢、碳水化合物代谢和能量代谢（ p < 0.05）。 此类研究对 IMI 引起的小鼠海马体和肝脏损伤提供了总体看法，并暗示了与小鼠早期代谢损伤相关的健康风险。