Investigation of coagulotoxicity of snake venom species from Viperidae family of medical importance in Brazil.

• Grant number: 21/07627-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): December 01, 2022
• Effective date (End): July 31, 2025
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Karen de Morais Zani
• Grantee: Nathália da Costa Galizio
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Snake envenomation is classified by the World Health Organization as a neglected tropical disease responsible for approximately 2.5 million envenomations and 150,000 deaths per year, especially in rural regions of Africa, Asia, Latin America and Oceania. In Brazil, the Viperidae family represents the most important group of snakes for public health, as they are responsible for most of the recorded snakebites. Among the effects resulting from these accidents, hemostatic disorders caused by the snake venoms from a wide variety of species are believed to play a central role in the pathophysiology of envenomation and prey capture. Snake venoms, especially those belonging to the Elapidae and Viperidae families, have several toxins that interact with the blood clotting cascade and with fibrinolytic system. The intraspecific variability of snake venoms associated with their functional diversity is particularly critical when considering their reactivity with antivenom. In view of the complexity of envenomation caused by snake species belonging to the Viperidae family and the relevance of these species to public health, a multifaceted study comparing the coagulotoxic profile of the venoms of these species and their intraspecific variability, as well as their neutralization by the antivenom is extremely important. Thus, the present project proposes the characterization of the coagulotoxic profile of individual venoms of snake species of genus Bothrops and Lachesis of major medical and ecological importance in different Brazilian regions. Since the 1980s, the most used way of evaluating the coagulant activity of snake venoms is through the determination of its "Minimum Coagulant Dose" (MCD). However, in this study we propose a more recent approach to characterize venom coagulotoxicity. We will evaluate, by thromboelastometry, not only the clotting time as an end point, but also the speed of clot formation and its resistance. Furthermore, we will evaluate the venom activity specific hemostatic system components (through the use of specific chromogenic substrates) and their dependence on calcium and phospholipids. These parameters will allow the characterization of inter- and intraspecific variations related to the coagulant (or anticoagulant) activity of snake venoms, even if subtle. Considering that the understanding of the inter- and intraspecific variations of snake venoms is of great pharmacological, ecological and evolutionary importance, the evaluation of the action of these variations in human envenomation is essential for the production and efficient use of antivenom, allowing a rational choice of specimens for the composition of venom pools for antivenom production.