Citation

Nielsen VG, Losada PA. Basic Clin. Pharmacol. Toxicol. 2016; 120(2): 207-212.

Affiliation

The Department of Anesthesiology, University of Arizona College of Medicine, Tucson, Arizona, USA.

Copyright

(Copyright © 2016, Nordic Pharmacological Society, Publisher John Wiley and Sons)

DOI

10.1111/bcpt.12654

PMID

27546530

Abstract

Since the introduction of antivenom administration over a century ago to treat venomous snake bite, it has been the most effective therapy for saving life and limb. However, this treatment is not always effective and not without potential life-threatening side effects. We tested a new paradigm to abrogate the plasmatic anticoagulant effects of fibrinogenolytic snake venom metalloproteinases by inhibiting these Zn(+2) -dependent enzymes directly with carbon monoxide exposure. Assessment of the fibrinogenolytic effects of venoms collected from the Arizona Black rattlesnake, Northern Pacific rattlesnake, Western cottonmouth, Eastern cottonmouth, Broad-banded copperhead and Southern copperhead on human plasmatic coagulation kinetics was performed with thrombelastography in vitro. Isolated exposure of all but one venom (Southern copperhead) to carbon monoxide significantly decreased the ability of the venoms to compromise coagulation. These results demonstrated that direct inhibition of transition metal containing venom enzymes by yet to be elucidated mechanisms (e.g., CO binding to Zn(+2) or displacing Zn(+2) from the catalytic site, CO binding to histidine residues) can in many instances significantly decrease fibrinogenolytic activity. This new paradigm of carbon monoxide-based inhibition of the anticoagulant effects of snake venom metalloproteinases could potentially diminish hemostatic compromise in envenomed patients until antivenom can be administered. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Language: en