Abstract
Snake envenomation can result in hemorrhage, local necrosis, swelling, and if not treated properly can lead to adverse systemic effects such as coagulopathy, nephrotoxicity, neurotoxicity, and cardiotoxicity, which can result in death. As such, snake venom metalloproteinases (SVMPs) and disintegrins are two toxic components that contribute to hemorrhage and interfere with the hemostatic system. Administration of a commercial antivenom is the common antidote to treat snake envenomation, but the high-cost, lack of efficacy, side effects, and limited availability, necessitates the development of new strategies and approaches for therapeutic treatments. Herein, we describe the neutralization ability of anti-disintegrin polyclonal antibody on the activities of isolated disintegrins, P-II/P-III SVMPs, and crude venoms. Our results show disintegrin activity on platelet aggregation in whole blood and the migration of the SK-Mel-28 cells that can be neutralized with anti-disintegrin polyclonal antibody. We characterized a SVMP and found that anti-disintegrin was also able to inhibit its activity in an in vitro proteolytic assay. Moreover, we found that anti-disintegrin could neutralize the proteolytic and hemorrhagic activities from crude Crotalus atrox venom. Our results suggest that anti-disintegrin polyclonal antibodies have the potential for a targeted approach to neutralize SVMPs in the treatment of snakebite envenomations.
Highlights
Snake venom is the combination of many different types of enzymatic and nonenzymatic proteins and can cause toxicity upon envenomation
We used a multi-step systematic approach to characterize and neutralize a disintegrin, PII/PIII snake venom metalloproteinases (SVMPs) and crude venom to determine the potential of our novel antibody
Based on our lab’s extensive analysis on disintegrins from Crotalus snakes, the native disintegrins isolated from C. atrox, C. horridus and C. s. scutulatus are 100 % identical (Figure 1E)
Summary
Snake venom is the combination of many different types of enzymatic and nonenzymatic proteins and can cause toxicity upon envenomation. In the USA, it is estimated that there are 10,000 snakebites per year that require emergency treatment [3]. Of those bites, it has been determined that 4500 of the envenomations are from the Crotalidae family [3]. The C. atrox, accounts for most envenomations within northern Mexico and the United States [5]. Venom toxicity from both C. atrox and C. o. One can suffer from severe pain, vomiting, edema [6,7] and fluctuation of blood pressure [8]
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