Proteomics and metabolomics systems analysis of envenomation by Bothrops snakes and antivenom effects using a murine model.

Abstract

Animal venoms comprise many toxins that act in concert to break apart the highly robust homeostatic systems of prey organisms. On the other hand, prey organisms actively antagonize each step of the envenomation phenomenon, which displays a complex kinetics involving important changes at molecular, cell, tissue and organism levels. The challenges for studying venoms and envenomation comprehend two hurdles: first, to analyze, isolate and chemically characterize the variety of toxin molecules in natural venoms; second, to uncover molecular mechanisms underlying the dynamics of envenomation, which includes systemic responses progressing from local cells and tissues up to the entire organism. In previous works, omics-style investigation of individual snake venom metalloproteinases (SVMP) activities on complex biological systems has allowed for the evaluation of several aspects of the pathology of the snake envenomation, as well as the in vivo effects triggered by SVMPs. In this context, the general aim of this project is expand the systems analysis of mammalian host response to complex toxins rather than individual components, by applying proteomics and metabolomics approaches to explore the in vivo effects of Bothrops jararaca venom in the muscle, plasma, kidneys, lungs and liver of mice. Considering the worldwide burden of snakebite death and disability, which is recognized by the WHO as a tropical neglected disease, and the crucial role of antivenom in its treatment, the impact of anti-bothropic antivenom in the systemic venom effects will also be evaluated. (AU)