Estrategias biotecnologicas como tratamentos alternativos nos acidentes escorpionicos

Abstract

Scorpionism is the most common envenomation-related accident in Brazil, with increasing incidence due to climate change, especially in densely populated areas. Current treatment relies on heterologous antivenoms produced by immunizing horses with crude Tityus serrulatus venom (TsV), but the high toxicity of this immunogen and the challenges of using crude venoms have driven the search for alternative strategies. In this project, we developed a recombinant chimeric multi-epitope protein (TsMEP) derived from ten linear B-cell epitopes of TsV hyaluronidase and voltage-gated sodium channel toxins, identified via SPOT-synthesis. TsMEP was shown to be non-toxic, and antibodies raised in rabbits displayed strong ELISA reactivity against venoms from Brazilian scorpions (T. serrulatus, T. bahiensis, T. obscurus, T. stigmurus) as well as Hadruroides lunatus (Peru) and Androctonus australis hector (North Africa). In vitro and in vivo neutralization assays demonstrated that anti-TsMEP antibodies partially inhibited TsV hyaluronidase activity and reduced lethality in mice. Another critical aspect of scorpionism is the role of hyaluronidase in facilitating venom spread from the sting site to the bloodstream and target organs, worsening the neurotoxic effects. As a first-aid approach, we developed an injectable in situ polymerizable hydrogel formulation combining carboxymethyl chitosan and aldehyde-modified hyaluronic acid with plant-derived polyphenols. This system was designed to inhibit TsV hyaluronidase activity while capturing TsV-polyphenol complexes and free toxins during polymerization. Our results showed significant reductions in venom circulation and target organ accumulation when the hydrogel was applied 10 minutes after venom injection, providing 100 % protection against a 2 LD₅₀ TsV dose in mice. While these approaches are innovative and promising, further research and extensive validation studies are required before implementation in scorpionism management.