Evaluation of the synergistic effects of Ts1, Ts2 and Ts6 neurotoxins from Tityus serrulatus venom on immune system modulation

• Grant number: 24/20361-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2025
• End date: December 31, 2025
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Francielle Almeida Cordeiro
• Grantee: Lorena de Oliveira Agati
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Scorpions are venomous arthropods belonging to the class Arachnida, with over 2,820 known species worldwide. Famous for the significant medical importance of their toxins, the family Buthidae includes about 48% of the known scorpion species, causing more than 1.2 million cases of envenomation annually. In Brazil, the main representative of this family is Tityus serrulatus, commonly known as the yellow scorpion, which is responsible for the majority of accidents involving venomous animals in the country. Since 2017, the number of scorpion stings in Brazil has exceeded 120,000 cases, representing a more than threefold increase over the past decade. The venom of T. serrulatus is primarily composed of neurotoxic proteins that modulate sodium and potassium channels (NaTx and KTx). Its action results in intense and prolonged neuronal depolarization, leading to excessive neurotransmitter release and causing disturbances in the sympathetic and parasympathetic autonomic nervous systems. Additionally, when neurotoxins are detected by the organism's pattern recognition receptors (PRRs), they trigger a local and systemic inflammatory response, promoting the activation of NF-¿B, c-Jun, and the NLRP3 inflammasome, which generates an acute inflammatory response characterized by the release of pro-inflammatory cytokines and the proliferation of macrophages. This project aims to isolate and evaluate the action of the toxins Ts1 (¿-NaTx), Ts2 (¿-NaTx), and Ts6 (¿-KTx), which act on sodium and potassium channels, using the Peritonitis model. This analysis will be conducted with the isolated toxins and their combinations to assess their synergistic action and expand our understanding of how they affect the cellular mediators responsible for inducing inflammation.