Decreased snake venom metalloproteinase effects via inhibition of enzyme and modification of fibrinogen

@article{Nielsen2016DecreasedSV,
  title={Decreased snake venom metalloproteinase effects via inhibition of enzyme and modification of fibrinogen},
  author={Vance G. Nielsen and Marco Cerruti and Olivia M. Valencia and Quinlan Amos},
  journal={BioMetals},
  year={2016},
  volume={29},
  pages={913-919}
}
Since the introduction of antivenom administration 120 years ago to treat venomous snake bit, it has been the gold standard for saving life and limb. However, this therapeutic approach 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 modification of fibrinogen with iron and carbon monoxide and by inhibiting these Zn2+ dependent… 

Iron protects porcine plasma coagulation kinetics from degradation by Crotalus atrox venom

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

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Data demonstrate indirectly that the biometal heme is likely bound to these disparate venoms as an intermediary modulatory molecule and may be a potential modulator of heme as a protective mechanism for venomous snakes against injury from their own proteolytic venoms.

Characterization of the Rabbit as an In Vitro and In Vivo Model to Assess the Effects of Fibrinogenolytic Activity of Snake Venom on Coagulation

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Role of heme modulation in inhibition of Atheris, Atractaspis, Causus, Cerastes, Echis, and Macrovipera hemotoxic venom activity

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Carbon monoxide inhibits the anticoagulant activity of phospholipase A2 purified from Crotalus adamanteus venom

  • V. Nielsen
  • Biology, Chemistry
    Journal of Thrombosis and Thrombolysis
  • 2018
Findings open the possibility that other PLA2 contained in snake venom with multiple toxicities may be heme bearing and CO-inhibitable, which have profound potential basic and clinical science implications.

Mechanisms Responsible for the Anticoagulant Properties of Neurotoxic Dendroaspis Venoms: A Viscoelastic Analysis

There was great species-specific variation in potency and mechanism(s) responsible for the anticoagulant activity of Dendroaspis venom, with perhaps all three protein classes—3-FTx, Kunitz-type SPI and metalloproteinases—playing a role in the venoms characterized.

CatroxMP-II: a heme-modulated fibrinogenolytic metalloproteinase isolated from Crotalus atrox venom

The first example of a snake venom metalloproteinase that is heme-bound and CO-inhibited is presented, and it is suggested that the biometal, heme, may be attached to venom enzymes and may be modulated by CO.

Crotalus atrox Venom Exposed to Carbon Monoxide Has Decreased Fibrinogenolytic Activity In Vivo in Rabbits

  • V. Nielsen
  • Biology, Medicine
    Basic & clinical pharmacology & toxicology
  • 2018
Future studies to determine whether rabbits injected with such venom subcutaneously/intramuscularly can have consequent coagulopathy abrogated by injection of carbon monoxide‐releasing molecules into the ‘bite site’ are justified are justified.

Effects of Heme Modulation on Ovophis and Trimeresurus Venom Activity in Human Plasma

A novel “venom kinetomic” approach has potential to identify clinically relevant enzymatic activity and assess efficacy of antivenoms between genetically and geographically diverse species.

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