Molecular characterization of the in vivo effects of Bothrops jararaca venom: analysis of mouse muscle tissue and plasma, by proteomic and immunohistochemical approaches

Abstract

Envenoming by viperid snakes is a critical public health problem in Brazil and is recognized by the World Health Organization (WHO) as one of the most important Neglected Tropical Diseases, causing a high percentage of permanent disability and, frequently, death. It is well established that systemic effects of envenomation by Bothrops snakes comprise hemorrhage, coagulopathy, shock, and renal failure. However, the molecular mechanisms involved in these effects are only partially known. On the other hand, it is recognized that these disorders are mainly promoted by snake venom metalloproteinases (SVMP), snake venom serine proteinases (SVSP), phospholipases A2 (PLA2), and C-type lectins (CTL). In this scenario, mass spectrometry-based proteomic analysis of local tissue and blood plasma, and immunohistochemical analysis are powerful approaches to integrate the findings of local and systemic effects in the pathogenesis induced by snake venoms. The proposal of post-doctoral training is to molecularly characterize the effects of Bothrops jararaca venom on the thigh muscle and blood plasma, in a murine model, using integrative technologies of mass spectrometry and immunodetection of tissue damage. In addition, by the same approaches, the impact of the anti-bothropic antivenom treatment after the venom injection, will also be evaluated in this model. (AU)