PLA2 Inhibitor Varespladib as an Alternative to the Antivenom Treatment for Bites from Nikolsky's Viper Vipera berus nikolskii.

Oleksandr Zinenko,Yevgen Korniyenko,Igor Tovstukha

doi:10.3390/toxins12060356

Abstract

Although envenoming by a small East European species of viper is rarely severe, and only exceptionally fatal, lack of specific antivenom stocks in a few areas within this region and possible severe side effects of antivenom application leave most bites to be treated only with antihistamines and supportive therapy. Varespladib is an effective inhibitor of snake phospholipase, and, as such, it could be considered as first-line therapy. The Nikolsky’s viper venom contains an extremely high concentration of phospholipase A2 (PLA2), responsible for the toxic effects of the venom, as well as minor amounts of other toxins. If Varespladib can successfully inhibit PLA2 activity, the Nikolsky’s viper could be one of the first venomous snakes having an antitoxin-specific treatment regimen. To assess that, Varespladib was administered alone subcutaneously to adult male CD-1 mice (8 mg/kg) and compared to mice exposed to Vipera berus nikolskii crude venom (8 mg/kg = 10 LD50) or a combination of Varespladib and the same amount of the venom. Experimental animals were monitored for the presence of envenoming symptoms and mortality for 48 h after injection. Eighty percent of mice receiving both Varespladib and venom survived, while 100% of the control group receiving venom alone died within 4 h. Experimental results are consistent with Varespladib acting as an effective antitoxin in the mouse model against Nikolsky’s viper venom. Further studies are needed under experimental conditions that more closely resemble natural envenoming (i.e., delayed administration).

Highlights

Snake bites are a global health problem, mostly in tropical countries
Our observations indicated that the main symptoms of envenoming by V. b. nikolskii consisted of local edema and pain, lymphangitis, and hypotension
Mice in the control group did not show any signs of pathology, and 100% of the animals survived through the duration of the experiment. This is the first time we tested the protective action of Varespladib against V. b. nikolskii venom

Summary

Introduction

Snake bites are a global health problem, mostly in tropical countries. It is estimated that about2.7 million people are envenomed annually, and hundreds of thousands die each year [1]. Snake bites are a global health problem, mostly in tropical countries. Health Organization listed snake bites as a category A neglected tropical disease, underlining the global significance of this problem. Disadvantages of antivenom therapy are the high or limited specificity of monovalent and polyvalent antivenoms, high production costs, the need for cold-chain delivery and storage, the requirement of professional supervised application, and a high risk for severe side effects [1]. These disadvantages hamper its use as a first-line treatment in remote settings or in areas with supply chain disruptions. There is a growing problem in many regions, especially in Africa, where antivenom supply specific for local snake species has decreased due to lack of commercial interest [1,3]

Methods

Results

Discussion

Conclusion