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Anticoagulant activity of krait, coral snake, and cobra neurotoxic venoms with diverse proteomes are inhibited by carbon monoxide

Nielsen, Vance G.a; Frank, Nathanielb; Turchioe, Brian J.a

Blood Coagulation & Fibrinolysis: December 2019 - Volume 30 - Issue 8 - p 379–384
doi: 10.1097/MBC.0000000000000842
ORIGINAL ARTICLES
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Background A phenomena of interest is the in vitro anticoagulant effects of neurotoxins found in elapid venoms that kill by paralysis. These enzymes include phospholipase A2 (PLA2), and it has recently been demonstrated that carbon monoxide inhibits the PLA2-dependent neurotoxin contained in Mojave rattlesnake type A venom. The purpose of this investigation was to assess if the anticoagulant activity of elapid venoms containing PLA2 and/or three finger toxins could be inhibited by carbon monoxide.

Methods Venoms collected from Bungarus multicinctus, Micrurus fulvius, and five Naja species were exposed to carbon monoxide via carbon monoxide releasing molecule-2 prior to placement into human plasma. Coagulation kinetics were assessed via thrombelastography.

Results Compared with plasma without venom addition, all venoms had significant anticoagulant effects, with a 160-fold range of concentrations having similar anticoagulant effects in a species-specific manner. Carbon monoxide significantly inhibited the anticoagulant effect of all venoms tested, but inhibition was not complete in all cases.

Conclusion Given that individual neurotoxin activity often depends on intact activity that includes anticoagulant action, it may be possible that carbon monoxide inhibits neurotoxicity. Future investigation is justified to assess such carbon monoxide mediated inhibition with purified neurotoxins in vitro and in vivo.

aThe Department of Anesthesiology, University of Arizona College of Medicine, Tucson, Arizona

bMtoxins, Oshkosh, Wisconsin, USA

Correspondence to Vance G. Nielsen, MD, The Department of Anesthesiology, University of Arizona College of Medicine, PO Box 245114, 1501 North Campbell Avenue, Tucson, AZ 85724-5114, USA. Tel: +1 520 626 7195; fax: +1 520 626 6943; e-mail: vgnielsen333@gmail.com

Received 4 June, 2019

Accepted 29 July, 2019

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