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Toxins (Basel) ; 13(4)2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33807363

RESUMO

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.


Assuntos
Anticorpos Neutralizantes/farmacologia , Antivenenos/farmacologia , Venenos de Crotalídeos/antagonistas & inibidores , Crotalus , Desintegrinas/antagonistas & inibidores , Metaloproteases/antagonistas & inibidores , Inibidores de Proteases/farmacologia , Mordeduras de Serpentes/tratamento farmacológico , Regulação Alostérica , Animais , Especificidade de Anticorpos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Reações Cruzadas , Venenos de Crotalídeos/enzimologia , Venenos de Crotalídeos/imunologia , Modelos Animais de Doenças , Desintegrinas/imunologia , Desintegrinas/metabolismo , Hemorragia/enzimologia , Hemorragia/etiologia , Hemorragia/prevenção & controle , Humanos , Metaloproteases/imunologia , Metaloproteases/metabolismo , Camundongos Endogâmicos BALB C , Agregação Plaquetária/efeitos dos fármacos , Mordeduras de Serpentes/sangue , Mordeduras de Serpentes/enzimologia , Mordeduras de Serpentes/imunologia
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