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Toxins (Basel) ; 13(4)2021 03 31.
Artículo en Inglés | MEDLINE | ID: mdl-33807363

RESUMEN

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.


Asunto(s)
Anticuerpos Neutralizantes/farmacología , Antivenenos/farmacología , Venenos de Crotálidos/antagonistas & inhibidores , Crotalus , Desintegrinas/antagonistas & inhibidores , Metaloproteasas/antagonistas & inhibidores , Inhibidores de Proteasas/farmacología , Mordeduras de Serpientes/tratamiento farmacológico , Regulación Alostérica , Animales , Especificidad de Anticuerpos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Reacciones Cruzadas , Venenos de Crotálidos/enzimología , Venenos de Crotálidos/inmunología , Modelos Animales de Enfermedad , Desintegrinas/inmunología , Desintegrinas/metabolismo , Hemorragia/enzimología , Hemorragia/etiología , Hemorragia/prevención & control , Humanos , Metaloproteasas/inmunología , Metaloproteasas/metabolismo , Ratones Endogámicos BALB C , Agregación Plaquetaria/efectos de los fármacos , Mordeduras de Serpientes/sangre , Mordeduras de Serpientes/enzimología , Mordeduras de Serpientes/inmunología
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