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Molecules 2018, 23(2), 391; https://doi.org/10.3390/molecules23020391

Exploration of the Inhibitory Potential of Varespladib for Snakebite Envenomation

School of Basic Medical Sciences, Nanchang University, Nanchang 330006, China
These authors contributed equally to this work.
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Author to whom correspondence should be addressed.
Received: 2 January 2018 / Revised: 8 February 2018 / Accepted: 9 February 2018 / Published: 12 February 2018
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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. View Full-Text
Keywords: antivenom; myotoxicity; phospholipase A2; varespladib antivenom; myotoxicity; phospholipase A2; varespladib
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Wang, Y.; Zhang, J.; Zhang, D.; Xiao, H.; Xiong, S.; Huang, C. Exploration of the Inhibitory Potential of Varespladib for Snakebite Envenomation. Molecules 2018, 23, 391.

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