Examination of the Efficacy and Cross-Reactivity of a Novel Polyclonal Antibody Targeting the Disintegrin Domain in SVMPs to Neutralize Snake Venom

Autor: Oscar Sanchez, Ilse Diego, Emelyn Salazar, Shelby Szteiter, Abcde Cirilo, Jonathan Ortegon, Jacob A. Galan, Montamas Suntravat, Armando Reyes, Elda E. Sánchez, Eliana M. Salinas
Rok vydání: 2021
Předmět:
Necrosis
Platelet Aggregation
Disintegrins
Health
Toxicology and Mutagenesis
Antivenom
lcsh:Medicine
Snake Bites
Venom
Pharmacology
Toxicology
medicine.disease_cause
Cross-reactivity
Antibody Specificity
Cell Movement
Mice
Inbred BALB C
0303 health sciences
biology
Antivenins
030302 biochemistry & molecular biology
disintegrin
Snake venom
medicine.symptom
Hemorrhage
Cross Reactions
complex mixtures
SVMP PII/PIII
Article
C. o. helleri
C. atrox
03 medical and health sciences
Allosteric Regulation
Cell Line
Tumor
anti-disintegrin
Crotalid Venoms
medicine
Disintegrin
Animals
Humans
Protease Inhibitors
Envenomation
Cell Proliferation
030304 developmental biology
antivenom
business.industry
lcsh:R
Crotalus
Antibodies
Neutralizing
carbohydrates (lipids)
Disease Models
Animal
Polyclonal antibodies
Metalloproteases
biology.protein
business
Zdroj: Toxins
Volume 13
Issue 4
Toxins, Vol 13, Iss 254, p 254 (2021)
ISSN: 2072-6651
Popis: 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.
Databáze: OpenAIRE
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