Changes in toxicity after mixing imidacloprid and cadmium: enhanced, diminished, or both? From a perspective of oxidative stress, lipid metabolism, and amino acid metabolism in mice

Imidacloprid (IMI) and cadmium (Cd) are pollutants of concern in the environment. Although investigations about their combined toxicity to organisms such as earthworms, aquatic worms, Daphnia magna , and zebrafish have been carried out, their combined toxicity to mammals remains unknow. In this study, twenty-four 8-week-old mice were arbitrarily separated into 4 groups: CK (control group), IMI (15 mg/kg bw/day, 1/10 LD50), Cd (15 mg/kg bw/day, 1/10 LD50), and IMI + Cd (15 mg/kg bw/day IMI + 15 mg/kg bw/d Cd) and the combined toxic effects of IMI and Cd were examined with biochemical (oxidative stress testing) and omics approaches (metabolomics and lipidomics). The results revealed changes in each treatment group in terms of oxidative stress, abnormalities in lipid metabolism, and disturbances in amino acid metabolism. Co-administration had antagonistic effects on MDA accumulation and lipid metabolism disorders while acting synergistically on changes in SOD and GSH-Px activities. It is worth noting that after analysis, the changes caused by mixed administration in vivo were closer to those caused by IMI administration alone. This study provides new insights into the combined toxicity of neonicotinoids and heavy metals, which is helpful for relevant environmental governance and further investigations about their impacts on human health and the environment.