Bothrops jararaca envenomation and neurotoxicity: Exploratory analysis of the brain proteome and peptidome after injection of B. jararaca venom in the gastrocnemius muscle of mice

Abstract

In Brazil, 90% of snakebites are caused by the genus Bothrops. Although it is well established that the systemic effects of envenoming include cardiovascular shock, coagulopathy and renal failure, the molecular mechanisms involved in these effects are still partially understood. Furthermore, complications related to the neurotoxicity of the venom, such as cerebral infarction, hemorrhagic and ischemic stroke, may occur in individuals after Bothrops envenomation, often resulting in a high percentage of deaths among victims. These clinical manifestations are caused, directly or indirectly, by toxins abundant in the venom, such as metalloproteinases, serine proteases, type C lectins and A2 phospholipases. There is a lack of studies on the neurotoxicity of B. jararaca venom, the most prevalent species and most responsible for snakebites in the South and Southeast regions of Brazil, although there are reports of strokes associated with the envenomation. In this scenario, proteomics and peptidomics analyses based on mass spectrometry has been applied as a powerful tool for understanding the effects related to the pathogenesis caused by snake venoms. Thus, the objective of the present project is to characterize the systemic effects of B. jararaca envenomation on the brain tissue of mice, whether or not subjected to injection of anti-bothropic antivenom, through analyzes using mass spectrometry approaches. In parallel, we intend to evaluate, at a proteomic level, the effects of bothropic venom on cells of the human central nervous system.