Twenty-four hours of Thiamethoxam: In vivo and molecular dynamics simulation study on the toxicokinetic and underlying mechanisms in quails (Coturnix japonica)

Abstract

Neonicotinoids is the most widely used insecticide, its contamination has led to sustained bird population declines. However, the toxicokinetic and underlying mechanisms of neonicotinoid toxicity in birds are largely unknown. Thiamethoxam (TMX), as a representative neonicotinoid insecticide, is now widely detected in most environmental medium and animal bodies. In this study, 5 mg/kg body weight TMX (potential environmental intake level) were orally administrated to male Japanese quails (Coturnix japonica). We found a rapid absorption, distribution, metabolism and elimination of TMX in quails in a period of 24 h, with the main metabolite, clothianidin (CLO), being extensively distributed and rapidly eliminated from tissues as well. The maximum plasm concentration of CLO was consistent with wild birds. Metabolomics analysis and followed determination of liver enzymes mRNA expression indicated the rapid metabolism was mediated mainly by CYPs and GSTs that involved riboflavin metabolism and glutathione metabolism pathways upon TMX exposure. Molecular dynamic simulation showed the strongest binding interaction in quail CYP2H1-TMX and CYP3A12-CLO complexes among a set of CYPs-substrate. The present study elucidated toxicokinetic and underlying metabolic mechanisms of TMX in quails at environmentally-relevant concentration, the findings would facilitate the understanding of potential risks of TMX and its metabolites to birds.

Keywords: Birds; Clothianidin (CLO); Cytochrome P450; Thiamethoxam (TMX); Toxicokinetics.