Differential Hematotoxic Activity of Southeast Asian Pit Viper Venoms: The Cross-Neutralizing Effect of Available Antivenoms

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  Image Credit: Creative Commons (some rights reserved) CC BY-NC Photo 111998430, (c) Nicholas Hess Differential Hematotoxic Activity of Southeast Asian Pit Viper Venoms: The Cross-Neutralizing Effect of Available Antivenoms Abstract Background/Objectives : Pit vipers (subfamily Crotalinae) are responsible for a large proportion of snakebite envenoming cases in Southeast Asia. Envenomation by these snakes commonly causes hematotoxic effects, including platelet dysfunction and coagulation disturbances. Although antivenom remains the mainstay of treatment, species-specific antivenoms are not available for several regional pit viper species. This study evaluated the hematotoxic activities of selected Southeast Asian pit viper venoms and the cross-neutralizing capacity of commercially available antivenoms.  Methods : Venoms from five medically important pit viper species— Calloselasma rhodostoma ,  Trimeresurus albolabris ,  T. hageni ,  T. purpureomaculatus , ...

Heparin-incorporated whey protein isolate-derived hydrogels with an intended dual function as snakebite wound dressings and drug delivery systems inhibit spitting cobra venom-induced cytotoxicity

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Heparin-incorporated whey protein isolate-derived hydrogels with an intended dual function as snakebite wound dressings and drug delivery systems inhibit spitting cobra venom-induced cytotoxicity

Abstract

Snakebite envenoming affects millions of people annually, with current treatments limited to animal-derived antivenoms. Repurposed drug-inhibitors of toxin families offer an exploitable avenue to improve snakebite treatment, including heparins which can inhibit cytotoxic three-finger toxins. However, to be effective therapies in-the-field such treatments must be engineered into drug delivery devices capable of rapidly administering drug(s) to the envenomation site. Herein we introduce the concept of integrating heparins, specifically unfractionated heparin (H) and its low molecular weight heparinoid variant, tinzaparin (T), into hydrogels composed of whey protein isolate (WPI), an inexpensive byproduct of the dairy industry that is cytocompatible, stiff, sterilizable by autoclaving, and that has the dual function of being able to locally deliver drugs and act as wound dressings. The aims of this research were to investigate whether heparin-containing WPI hydrogels displayed physical characteristics suitable for wound dressings and could effectively release drug in sufficient quantities to inhibit the cytotoxic activity of spitting cobra venom. To do so, five hydrogel prototypes were produced: 40% WPI no drug control, and 5% H, 10% H, 5% T, and 10% T all within 40% WPI hydrogels. It was determined that heparins successfully integrated into WPI hydrogels and heparin-containing WPI hydrogels exhibited improved swelling versus the 40% WPI no drug control, suggesting improved absorption of wound exudate; however, this heparin integration also increased the hydrogel degradation rate in simulated wound environments. Most importantly, sufficiently high concentrations of T were released into phosphate buffered saline from the 10% T hydrogels to neutralise Naja nigricollis venom cytotoxicity in a HaCaT cell cytotoxicity model. Together, our results suggest that the integration and diffusion of venom-inhibiting drugs in WPI hydrogels is possible and that the development of such drug-integrated hydrogels into snakebite wound dressings warrants further research.
Gray, M. J., Baines, D. K., De Castro, G., Cobb, T., Tyrrell, L. A., Hyam, S. J., Smith, A. M., Casewell, N. R., Allinson, S. L., Douglas, T. E., & Hall, S. R. (2026). Heparin-incorporated whey protein isolate-derived hydrogels with an intended dual function as snakebite wound dressings and drug delivery systems inhibit spitting cobra venom-induced cytotoxicity. Toxicon, 109061. https://doi.org/10.1016/j.toxicon.2026.109061