Livers of Male Coturnix japonica treated by thiamethoxam

Thiamethoxam (TMX) is one of the major neonicotinoids, which is widely-used for seed coating. The consumption of TMX-coated seeds posed threat to birds during crop sowing. The hepatotoxicity of TMX has been reported in mammals, however, no clear evidences showed toxicity effects on bird livers induced by TMX. In this study, male Japanese quails (Coturnix japonica) were exposed to 20 or 200 mg/kg TMX-treated bird feed for 28 day. Results showed that ingestion of TMX-treated diet resulted in accumulation of Clothianidin (CLO) in quail plasma and liver, and induced inflammatory cell infiltration in quail liver. Oxidative stress-related biological processes were significantly enriched in both two TMX treatment group. Moreover, multi-omics analysis indicated ferroptosis and DNA damage was implicated in hepatotoxicity caused by high- and low- concentration TMX exposure, respectively. TMX treatment decreased CAT activity and GSH concentration, and increased expression of ferroptosis-related gene. In addition, the up-regulation of 8-OHdG concentration and DNA repair-related genes expression demonstrated low-dose TMX-triggered oxidative DNA damage. The present results highlight hepatotoxicity of TMX on bird livers, and contribute to deep understanding of TMX toxicity mechanism for birds.