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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\u2005\u00b5g of melittin (\u2248LD20). 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.<\/jats:p>","DOI":"10.1242\/jeb.251886","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T08:46:01Z","timestamp":1772786761000},"source":"Crossref","is-referenced-by-count":2,"title":["Self-toxicity and tolerance mechanisms of honeybee venom in honeybees"],"prefix":"10.1242","volume":"229","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9983-7633","authenticated-orcid":false,"given":"Jan","family":"\u010cern\u00fd","sequence":"first","affiliation":[{"name":"Institute of Entomology, Biology Centre, CAS 1 , Brani\u0161ovsk\u00e1 31, 370 05 \u010cesk\u00e9 Bud\u011bjovice ,","place":["Czech Republic"]},{"name":"University of South Bohemia 2 Faculty of Science , , Brani\u0161ovsk\u00e1 31, 370 05 \u010cesk\u00e9 Bud\u011bjovice ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark\u00e9ta","family":"Hejn\u00edkov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Entomology, Biology Centre, CAS 1 , Brani\u0161ovsk\u00e1 31, 370 05 \u010cesk\u00e9 Bud\u011bjovice ,","place":["Czech Republic"]},{"name":"University of South Bohemia 2 Faculty of Science , , Brani\u0161ovsk\u00e1 31, 370 05 \u010cesk\u00e9 Bud\u011bjovice ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7501-6205","authenticated-orcid":false,"given":"\u0160\u00e1rka","family":"Podlahov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Entomology, Biology Centre, CAS 1 , Brani\u0161ovsk\u00e1 31, 370 05 \u010cesk\u00e9 Bud\u011bjovice ,","place":["Czech Republic"]},{"name":"University of South Bohemia 2 Faculty of Science , , Brani\u0161ovsk\u00e1 31, 370 05 \u010cesk\u00e9 Bud\u011bjovice ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2372-4848","authenticated-orcid":false,"given":"Radmila","family":"\u010capkov\u00e1 Frydrychov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Entomology, Biology Centre, CAS 1 , Brani\u0161ovsk\u00e1 31, 370 05 \u010cesk\u00e9 Bud\u011bjovice ,","place":["Czech Republic"]},{"name":"University of South Bohemia 3 Faculty of Agriculture and Technology , , Studentsk\u00e1 1668, 370 05 \u010cesk\u00e9 Bud\u011bjovice ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michala","family":"S\u00e1bov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Entomology, Biology Centre, CAS 1 , Brani\u0161ovsk\u00e1 31, 370 05 \u010cesk\u00e9 Bud\u011bjovice ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9850-4044","authenticated-orcid":false,"given":"Helena","family":"\u0160t\u011brbov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Entomology, Biology Centre, CAS 1 , Brani\u0161ovsk\u00e1 31, 370 05 \u010cesk\u00e9 Bud\u011bjovice ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6109-1979","authenticated-orcid":false,"given":"Dalibor","family":"Kodr\u00edk","sequence":"additional","affiliation":[{"name":"Institute of Entomology, Biology Centre, CAS 1 , Brani\u0161ovsk\u00e1 31, 370 05 \u010cesk\u00e9 Bud\u011bjovice ,","place":["Czech Republic"]},{"name":"University of South Bohemia 2 Faculty of Science , , Brani\u0161ovsk\u00e1 31, 370 05 \u010cesk\u00e9 Bud\u011bjovice ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"key":"2026032606394513000_JEB251886C1","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/0305-1978(92)90040-K","article-title":"Biochemical defense of pro-oxidant plant allelochemicals by herbivorous insects","volume":"20","author":"Ahmad","year":"1992","journal-title":"Biochem. 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