A study led by the Universitat Autònoma de Barcelona (UAB) shows that bee venom, apitoxin, alters the functioning of blood vessels, even at low concentrations. It also identified an important molecular pathway of oxidative stress involved in this effect, which in turn opens the door to exploring its therapeutic potential.
The work was carried out by a research team led by Francesc Jiménez Altayó, researcher at the Department of Pharmacology, Therapeutics and Toxicology at the UAB, and has been published in Toxicological Sciences, the official journal of the US Society of Toxicology. Researchers from the University of Barcelona, the University of Havana and the Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV) and Centro de Enfermedades Neurodegenerativas (CIBERNED) of the Instituto de Salud Carlos III were also involved.
Apitoxin is a mixture of bioactive molecules with melittin as its main component. Its therapeutic potential is increasingly recognised for some conditions, but its application is limited due to safety concerns. Beyond anaphylactic shock and renal failure, bee (Apis mellifera L.) stings are also associated with cardiovascular damage, especially in cases of poisoning resulting from a large number of stings. However, their effect on the vascular system (comprising the cardiovascular and lymphatic systems) and the mechanisms involved have not been sufficiently explored.
In the published study, the research team analyses the impact of apitoxin and melittin on human endothelial cells, which line the inner wall of blood and lymphatic vessels, and smooth muscle cells, and on the aortic artery in mice. The findings reveal that both compounds impact cell viability and endothelial relaxation capacity, leading to reduced vessel dilation.
“Vascular alterations occurred with doses of apitoxin that can be reached after multiple bee stings, but could occur even after a few stings in vulnerable individuals”,says Francesc Jiménez Altayó, UAB researcher and coordinator of the study.
The effects on the aorta were more severe in male mice, “possibly due to the protective effect of oestrogens on females, which reduces cardiovascular risk, although more studies are needed to confirm this idea”, explains Ángel Bistué, associate professor at the UAB and first author of the article.
The study shows that melittin represents almost half of bee venom (43.8%). However, despite being the component most associated with toxic effects, it does not act in exactly the same way as the whole venom, indicating that other substances in apitoxin also contribute.
Potential benefits to study
The research team also found that the negative effects of bee venom are due to an increase in oxidative stress and changes in nitric oxide, a molecule that regulates the dilation of blood vessels. This underlines the dual role of apitoxin for the vascular system, both as a toxic substance and as a potential therapeutic agent.
“The discovery shows that bee venom can be toxic to blood vessels, especially because it generates oxidative stress, but it also opens the door to possible therapeutic uses in some vascular disorders and other diseases, such as cancer. In this case, it could help regulate nitric oxide, which controls how blood vessels open and close inside some tumours, a factor that can influence both tumour growth and response to treatment”, says Jiménez Altayó. ”However, further studies are needed to confirm whether it can really have these medical applications”, he concludes.