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

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.

Effects of Imidacloprid and Gestational Age on Biodistribution and Maternal Toxicity in Pregnant Mice Compared to Non- Pregnant

“…In addition, the risk of exposure to the imidacloprid was also increased by maternal exposure on organogenesis critical period. These results are in consistent with the data reported that there was a significant decrease in the body weight gain of mice in the high dose group of 20 mg/kg/day (Zheng, et al, 2020). In similar, significant toxic symptoms, together with significant decrease in weight gain appeared in rats exposed to 20 mg/kg/day of IMI (Kapoor, et al, 2011).…”

Neurotoxic Effects of Neonicotinoids on Mammals: What Is There beyond the Activation of Nicotinic Acetylcholine Receptors?—A Systematic Review

“…Conditions of oxidative stress and neuroinflammation, mitochondrial damage, alterations in neurotransmitter systems, as well as changes in energy metabolism induced by NN pesticides can eventually lead to neuronal death. Some of the studies included here agree that both acute and chronic treatment with IMI and ACE pesticides caused DNA damage and neuronal degeneration, especially affecting the hippocampus [15,60,70,112,155].…”

“…It has also been shown that exposure to NN pesticides decreased neurogenesis in the dentate gyrus of the hippocampus and promoted apoptosis in this brain structure [66,111,112]. The dentate gyrus is one of the few brain areas where neurogenesis continues to occur during adulthood [113].…”

“…Thus, strict regulation of cellular energy metabolism is essential to ensure normal brain function, and any alteration in this can be associated with the development of various pathologies [187,188]. Some in vitro and in vivo investigations have shown that both shortand long-term exposure to IMI and CLO pesticides altered the metabolism and energy balance of rodent brain cells, especially in the hippocampus [112,189]. These changes could reflect the metabolic plasticity of brain cells, that is, an attempt by brain cells to adapt their metabolism to the adverse conditions generated by NN pesticides.…”

Safety of high‐dose Puerariae Lobatae Radix in adolescent rats based on metabolomics

“…For the aminoacyl‐tRNA biosynthesis and steroid hormone biosynthesis pathways, ‐log(p) > 2 and pathway impact < 0.1 indicated that pathway interference is limited. For the phenylalanine, tyrosine, and tryptophan biosynthesis and phenylalanine metabolism pathways, ‐log(p) > 2 and pathway impact > 0.1 indicate strong pathway interference, suggested that PLR effects liver function, mainly via the inhibition of the conversion of phenylalanine to tyrosine and tryptophan or the inhibition of phenylalanine metabolism (Xu et al., 2012; Zheng et al., 2020).…”