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Ruthenium Antivenom Inhibits the Defibrinogenating Activity of Crotalus adamanteus Venom in Rabbits
1Department of Anesthesiology, The University of Arizona College of Medicine, Tucson, AZ 85724, USA.
International Journal of Molecular Sciences
|June 27, 2024
Summary
Eastern Diamondback rattlesnake venom causes bleeding disorders by affecting fibrinogen. A novel ruthenium antivenom effectively reversed these coagulopathic effects in a rabbit model, showing promise for treatment.
Area of Science:
- Toxicology and Pharmacology
- Hematology and Coagulation
Background:
- Eastern Diamondback rattlesnake (Crotalus adamanteus) envenomation presents a significant medical emergency in the Southeastern United States.
- Snake venom thrombin-like enzyme (SVTLE) in the venom causes defibrinogenation, leading to coagulopathy (bleeding disorders) without impacting human platelets.
Purpose of the Study:
- To kinetically document the coagulopathy induced by SVTLE at a molecular level using thrombelastographic methods.
- To evaluate the efficacy of a novel ruthenium compound-based site-directed antivenom in abrogating these envenomation-induced coagulopathic effects.
Main Methods:
- Utilized thrombelastographic analysis of whole blood samples in a rabbit model of envenomation.
- Assessed coagulation kinetics with and without platelet inhibition.
- Administered a novel ruthenium compound containing site-directed antivenom.
Main Results:
- Documented the kinetic coagulopathy induced by SVTLE on fibrinogen-dependent coagulation.
- The ruthenium antivenom completely abrogated coagulopathic effects in whole blood without platelet inhibition.
- Significantly diminished coagulation loss in platelet-inhibited samples, confirming antivenom efficacy.
Conclusions:
- Provided crucial coagulation kinetic insights into SVTLE's molecular interactions and effects on fibrinogen.
- Confirmed the therapeutic efficacy of the novel ruthenium antivenom against rattlesnake envenomation-induced coagulopathy.
- Established a rationale for investigating other venoms and assessing site-directed antivenoms using this model.
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