Metabolic disturbance in hippocampus and liver of mice: A primary response to imidacloprid exposure

Meilin Zheng,Qin Liu,Hong Xiao,Shaohua Zeng,Qizhong Qin,Jieying Gao,Wenli Zhou,Qunhua Bai

doi:10.1038/s41598-020-62739-9

Abstract

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.

Highlights

Neonicotinoids are one new chemical class of insecticides developed and applied in the 1990s, following organophosphorus, carbamate and pyrethroid insecticides
The results showed that there was no difference in initial body weight of mice among the control group, the low-dose group and the high-dose group
The histopathological, biochemical and metabolic alterations induced by oral administration of two doses of IMI (5 and 20 mg/kg/day) for 28 days on hippocampus and liver of mice were studied

Summary

Introduction

Neonicotinoids are one new chemical class of insecticides developed and applied in the 1990s, following organophosphorus, carbamate and pyrethroid insecticides. A large number of literatures have described metabolomics studies in toxic effects induced by environmental pollutants, such as perfluorinated compounds[25,26], pesticide residues[27,28], heavy metals[29], and nanoparticles[30]. Tufi et al.[28] employed metabolomics to explore IMI-induced toxicity in the central nervous system of the freshwater snail and pointed out a disruption of neuronal metabolism. They found a turnover increase between choline and acetylcholine and proposed a hypothesis of an increase in the cholinergic gene expression. Until now, no systematic metabolomics studies on mammals exposed to IMI have been reported

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Results

Conclusion