Self-toxicity and tolerance mechanisms of honeybee venom in honeybees.

Honeybee venom (apitoxin) is a potent mixture of biologically active peptides and enzymes, primarily evolved as a defence against insect predators - including other bees. Recent evidence suggests that honeybees also employ components of apitoxin for both external and internal defence against parasites and microbial infections. Consequently, they are predicted to exhibit a remarkable resistance to their own venom, which they frequently encounter within colonies. To investigate this phenomenon, we examined the physiological responses of honeybee workers and drones to envenomation. Individuals were injected with a crude venom dose equivalent to 7.1 µg of melittin (≈LD20). Venom exposure significantly affected multiple physiological parameters, including the levels and gene expression of adipokinetic hormone and vitellogenin, antioxidative markers, lipofuscin accumulation and haemolymph arginine kinase concentration. Ultrastructural analyses further revealed profound alterations in thoracic muscle, including mitochondrial and myofibrillar degradation. Notably, workers and drones exhibited distinct physiological responses to venom. Our results indicate that honeybees mount a complex, multi-level defence to their own toxin, highlighting their potential as a unique model for studying endogenous anti-toxin mechanisms. Insights from this system may inspire future biomedical and biotechnological applications.