Biochemical, histopathological and untargeted metabolomic analyses reveal hepatotoxic mechanism of acetamiprid to Xenopus laevis

Acetamiprid, a commonly detected neonicotinoid in aquatic ecosystems, poses a threat to aquatic non-target organisms. However, limited information is available on the toxic effects of acetamiprid on nontarget aquatic organisms. This study assessed the toxic effects of acetamiprid on Xenopus laevis, a typical model organism. The acute toxicity for 96 h revealed that acetamiprid had detrimental effects with a median lethal concentration (LC50) value of 64.48 mg/L. Toxicity assays, including oxidative stress, histopathology and untargeted metabolomics of acetamiprid to X. laevis, were performed for 28 d at 1/10 and 1/100 LC50 by studying the liver, which is the most antioxidant and major metabolic organ. The results demonstrated that acetamiprid exposure significantly changed the oxidant status of and caused histological damage to the liver. Furthermore, the untargeted metabolomic analysis based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified the endogenous metabolites that were significantly altered. There were 89 differential metabolites compared to the controls: 64 in the 1/10 LC50 group, 47 in the 1/100 LC50 group, and 23 metabolites in the 1/10 LC50 group were the same as those in the 1/100 LC50 group. Sixteen pathways that were mainly associated with amino acid metabolism and lipid metabolism, such as sphingolipid metabolism, glycerophospholipid metabolism and histidine metabolism, were disrupted, revealing the hepatotoxic effects of acetamiprid on X. laevis at the molecular level. These findings provide crucial information for evaluating the aquatic risks of neonicotinoids.