Multi-omics approach to address the systemic effects of Bothrops jararaca venom in a murine model

Abstract

Snakebite envenomation is recognized in category A of the Neglected Tropical Diseases by the World Health Organization (WHO) due to the worldwide burden of snakebite death and disability. Although the local effects of bites are well documented, knowledge on the systemic effects of snake venoms is limited. Envenomation by Viperidae snakes causes hypotension, ultimately leading to shock, coagulopathy, and kidney failure, but the mechanisms behind these effects remain broadly unknown. This mismatch between clinical and mechanistic knowledge makes it hard to find better interventions for severe envenoming systemic effects. Using an integrative approach, including quantitative proteomics, N-terminomics, phosphoproteomics, and histopathology, in animals that received or not bothropic antivenom after Bothrops jararaca venom injection in the thigh muscle, we will analyze altered pathways in kidneys, liver, and lungs, with a special focus on the activity of venom proteolytic enzymes. This proposal has clear objectives of in-depth characterizing the systemic impact of Bothrops snake venom on mouse physiology using state-of-the-art proteomics-based methods and histopathology approaches and evaluating the impact of antivenom treatment. The expected results should shed light on the complex pathophysiology of venom-induced tissue damage and generate a better understanding of how snakebite envenoming may be treated in the future, regarding toxin neutralization and tissue regeneration. (AU)