{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T11:58:33Z","timestamp":1782734313666,"version":"3.54.5"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Agencia Estatal de Investigaci\u00f3n of Spain"},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Bee venom (apitoxin) is a mixture of bioactive molecules, with melittin as its principal component. Although its therapeutic potential is increasingly recognized, its toxic effects on vascular homeostasis remain underexplored. We investigated the impact of apitoxin and melittin on vascular cell viability and mouse aortic function. Cytotoxicity was assessed in cultured endothelial and smooth muscle cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Aortic function was evaluated by mounting thoracic aortas from young male and female C57BL\/6J mice in tissue baths. Isometric tension was measured during phenylephrine-induced contractions, as well as endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside) relaxations. To evaluate the roles of nitric oxide (NO) and oxidative stress, we used the NO synthase inhibitor N\u03c9-nitro-L-arginine methyl ester (L-NAME) and the antioxidant superoxide dismutase (SOD), respectively. High-performance liquid chromatography analysis revealed that melittin comprised 43.80% of apitoxin. Both apitoxin and melittin exhibited concentration-dependent cytotoxicity, significantly reducing endothelial cell viability at concentrations \u22655\u2009\u00b5g\/ml, whereas smooth muscle cells were affected at lower concentrations (\u22652.5\u2009\u00b5g\/ml for apitoxin; \u22651.5\u2009\u00b5g\/ml for melittin). In functional experiments, apitoxin enhanced phenylephrine-induced contractions at 1\u2009\u00b5g\/ml and impaired both endothelium-dependent and -independent relaxations at \u22650.1\u2009\u00b5g\/ml, particularly in males. Although melittin mimicked these effects, higher concentrations (\u22655\u2009\u00b5g\/ml) were required, suggesting that other venom components contribute to the vascular functional toxicity of apitoxin. L-NAME and SOD prevented apitoxin-induced vascular impairments, implicating the NO pathway and oxidative stress. These findings demonstrate that apitoxin impairs vascular cell viability and aortic function at clinically relevant concentrations, underscoring both its vascular risks and therapeutic potential.<\/jats:p>","DOI":"10.1093\/toxsci\/kfaf086","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T07:37:41Z","timestamp":1749541061000},"page":"196-207","source":"Crossref","is-referenced-by-count":1,"title":["Bee venom disrupts vascular homeostasis: apitoxin and melittin trigger vascular cell toxicity and aortic dysfunction in mice"],"prefix":"10.1093","volume":"207","author":[{"given":"\u00c0ngel","family":"Bistu\u00e9-Rovira","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Therapeutics, and Toxicology, Universitat Aut\u00f2noma de Barcelona , 08193 Cerdanyola del Vall\u00e8s (Barcelona),","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montse","family":"Sol\u00e9","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Universitat Aut\u00f2noma de Barcelona , 08193 Cerdanyola del Vall\u00e8s (Barcelona),","place":["Spain"]},{"name":"Institute of Neurosciences, Universitat Aut\u00f2noma de Barcelona , 08193 Cerdanyola del Vall\u00e8s (Barcelona),","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III , Madrid,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateu","family":"Anguera-Tejedor","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Therapeutics, and Toxicology, Universitat Aut\u00f2noma de Barcelona , 08193 Cerdanyola del Vall\u00e8s (Barcelona),","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bel\u00e9n","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Therapeutics, and Toxicology, Universitat Aut\u00f2noma de Barcelona , 08193 Cerdanyola del Vall\u00e8s (Barcelona),","place":["Spain"]},{"name":"Institute of Neurosciences, Universitat Aut\u00f2noma de Barcelona , 08193 Cerdanyola del Vall\u00e8s (Barcelona),","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Garc\u00eda-Tercero","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Therapeutics, and Toxicology, Universitat Aut\u00f2noma de Barcelona , 08193 Cerdanyola del Vall\u00e8s (Barcelona),","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"D\u00edaz-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Therapeutics, and Toxicology, Universitat Aut\u00f2noma de Barcelona , 08193 Cerdanyola del Vall\u00e8s (Barcelona),","place":["Spain"]},{"name":"Institute of Neurosciences, Universitat Aut\u00f2noma de Barcelona , 08193 Cerdanyola del Vall\u00e8s (Barcelona),","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zonia","family":"Mart\u00ednez-Benitez","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Instituto de Farmacia y Alimentos (IFAL), Universidad de La Habana , 10400 La Habana, Republic of Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7051-7871","authenticated-orcid":false,"given":"Ren\u00e9","family":"Delgado-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Therapeutics, and Toxicology, Universitat Aut\u00f2noma de Barcelona , 08193 Cerdanyola del Vall\u00e8s (Barcelona),","place":["Spain"]},{"name":"Department of Pharmacy, Instituto de Farmacia y Alimentos (IFAL), Universidad de La Habana , 10400 La Habana, Republic of Cuba"},{"name":"Department of Pharmacy and Pharmaceutical Technology, and Physical Chemistry, Faculty of Pharmacy and Food Sciences, Universitat de Barcelona , 08028 Barcelona,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9034-2041","authenticated-orcid":false,"given":"Francesc","family":"Jim\u00e9nez-Altay\u00f3","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Therapeutics, and Toxicology, Universitat Aut\u00f2noma de Barcelona , 08193 Cerdanyola del Vall\u00e8s (Barcelona),","place":["Spain"]},{"name":"Institute of Neurosciences, Universitat Aut\u00f2noma de Barcelona , 08193 Cerdanyola del Vall\u00e8s (Barcelona),","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III , 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