Synergistic impacts of flupyradifurone and uniconazole on oxidative stress biomarkers and immune-related gene expression in honey bees

The widespread application of pesticides in modern agriculture has been recognized as a key driver of declines in honey bee populations. Butenolide insecticide flupyradifurone (FLU) and triazole-based plant growth regulator uniconazole (UNI) are frequently found together in agricultural ecosystems, raising serious concerns about their combined toxicological impacts on pollinators. FLU and UNL mixture elicited an acute synergistic toxic effect on A. mellifera , significantly enhancing physiological stress. Enzymatic activity assays revealed notable alterations in the levels of superoxide dismutase (SOD), catalase (CAT), polyphenol oxidase (PPO), and glutathione S-transferase (GST), indicative of intensified oxidative stress, impaired detoxification mechanisms, and compromised immune function. Furthermore, transcriptomic analyses showed that the expression of five key genes, abaecin , domeless , relish , vitellogenin ( vtg ), and CRBXase , was more profoundly affected under combined exposure compared to individual treatments, highlighting disruptions in immune regulation, longevity pathways, and detoxification processes at the molecular level. These results provided compelling evidence that the co-occurrence of FLU and UNI posed a heightened biochemical and genetic threat to honey bees, likely due to synergistic interactions that amplified their individual toxicities. This study offered crucial insights into the ecological hazards of pesticide combinations. Such informed approaches are vital for minimizing pollinator risk and safeguarding ecosystem services essential to sustainable agriculture.