A fingerprint of plasma proteome alteration after local tissue damage induced by Bothrops leucurus snake venom in mice

Abstract

Bothrops spp. is responsible for about 70% of snakebites in Brazil, causing a diverse and complex pathophysiological condition. Bothrops leucurus is the main species of medical relevance found in the Atlantic coast in the Brazilian Northeast region. The pathophysiological effects involved B. leucurus snakebite as well as the organism's reaction in response to this envenoming, it has not been explored yet. Thus, edema was induced in mice paw using 1.2, 2.5, and 5.0 μg of B. leucurus venom, the percentage of edema was measured 30 min after injection and the blood plasma was collected and analyzed by shotgun proteomic strategy. We identified 80 common plasma proteins with differential abundance among the experimental groups and we can understand the early aspects of this snake envenomation, regardless of the suggestive severity of an ophidian accident. The results showed B. leucurus venom triggers a thromboinflammation scenario where family's proteins of the Serpins, Apolipoproteins, Complement factors and Component subunits, Cathepsins, Kinases, Oxidoreductases, Proteases inhibitors, Proteases, Collagens, Growth factors are related to inflammation, complement and coagulation systems, modulators platelets and neutrophils, lipid and retinoid metabolism, oxidative stress and tissue repair. Our findings set precedents for future studies in the area of early diagnosis and/or treatment of snakebites. Significance: The physiopathological effects that the snake venoms can cause have been investigated through classical and reductionist tools, which allowed, so far, the identification of action mechanisms of individual components associated with specific tissue damage. The currently incomplete limitations of this knowledge must be expanded through new approaches, such as proteomics, which may represent a big leap in understanding the venom-modulated pathological process. The exploration of the complete protein set that suffer modifications by the simultaneous action of multiple toxins, provides a map of the establishment of physiopathological phenotypes, which favors the identification of multiple toxin targets, that may or may not act in synergy, as well as favoring the discovery of biomarkers and therapeutic targets for manifestations that are not neutralized by the antivenom.