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Exploration of the Inhibitory Potential of Varespladib for Snakebite Envenomation
- Source :
- Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry, Molecules; Volume 23; Issue 2; Pages: 391, Molecules, Vol 23, Iss 2, p 391 (2018)
- Publication Year :
- 2018
- Publisher :
- MDPI, 2018.
-
Abstract
- Phospholipase A2s (PLA2) is a major component of snake venom with diverse pathologic toxicities and, therefore, a potential target for antivenom therapy. Varespladib was initially designed as an inhibitor of mammal PLA2s, and was recently repurposed to a broad-spectrum inhibitor of PLA2 in snake venom. To evaluate the protective abilities of varespladib to hemorrhage, myonecrosis, and systemic toxicities that are inflicted by different crude snake venoms, subcutaneous ecchymosis, muscle damage, and biochemical variation in serum enzymes derived from the envenomed mice were determined, respectively. Varespladib treatment showed a significant inhibitory effect to snake venom PLA2, which was estimated by IC50 in vitro and ED50 in vivo. In animal models, the severely hemorrhagic toxicity of D. acutus and A. halys venom was almost fully inhibited after administration of varespladib. Moreover, signs of edema in gastrocnemius muscle were remarkably attenuated by administration of varespladib, with a reduced loss of myonecrosis and desmin. Serum levels of creatine kinase, lactate dehydrogenase isoenzyme 1, aspartate transaminase, and alanine transaminase were down-regulated after treatment with varespladib, which indicated the protection to viscera injury. In conclusion, varespladib may be a potential first-line drug candidate in snakebite envenomation first aid or clinical therapy.
- Subjects :
- 0301 basic medicine
Indoles
Antivenom
Ecchymosis
Pharmaceutical Science
Snake Bites
Venom
Pharmacology
Acetates
Analytical Chemistry
chemistry.chemical_compound
Mice
Drug Discovery
Medicine
Edema
Creatine Kinase
biology
Antivenins
Alanine Transaminase
Keto Acids
Isoenzymes
Chemistry (miscellaneous)
Snake venom
Molecular Medicine
Female
antivenom
myotoxicity
phospholipase A2
varespladib
Phospholipase A2 Inhibitors
Myotoxin
Aspartate transaminase
complex mixtures
Article
lcsh:QD241-441
03 medical and health sciences
lcsh:Organic chemistry
Crotalid Venoms
Animals
Aspartate Aminotransferases
Physical and Theoretical Chemistry
Envenomation
Muscle, Skeletal
L-Lactate Dehydrogenase
business.industry
Organic Chemistry
Phospholipases A2
030104 developmental biology
chemistry
Alanine transaminase
biology.protein
Varespladib
business
Crotalinae
Subjects
Details
- Language :
- English
- ISSN :
- 14203049
- Volume :
- 23
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry
- Accession number :
- edsair.doi.dedup.....3b8bcb9838cd389c7792990e5eaffb71