Melatonin modulates redox balance, immune signalling, and midgut ultrastructure during cadmium oxide nanoparticle‐induced stress in honey bees

Cadmium oxide nanoparticles (CdO NPs) impose oxidative and cellular stress in honey bees ( Apis mellifera ) by disrupting redox homeostasis and epithelial integrity. We examined biochemical, molecular and cellular responses to CdO NPs and evaluated melatonin as a physiological modulator. Newly emerged workers were pre‐treated with melatonin (5, 50 or 500 ng/mL) for 10 days and then exposed to a sublethal CdO NP concentration (0.01 mg/mL; 20% LC 50 ) for 10 days. CdO NP exposure increased mortality (hazard ratio = 3.63), elevated midgut lipid peroxidation, altered antioxidant (SOD, GSTD, CAT, POD) and immune‐related (vitellogenin, hymenoptaecin, defensin‐1) gene expression and caused pronounced histopathological and ultrastructural changes, including disrupted microvilli and cytoplasmic disorganization. Melatonin pre‐treatment mitigated these effects in a concentration‐dependent manner, reducing oxidative damage, normalizing gene expression, preserving midgut architecture and improving survival to near‐control levels. These results indicate that melatonin stabilizes redox balance and cellular organization under metal‐induced stress, providing mechanistic insight into gut‐centred physiological resilience in insects.