Effects of iron and carbon monoxide on Lachesis muta muta venom-mediated degradation of plasmatic coagulation

Vance G Nielsen, R. W. Matika

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Hypofibrinogenemia is an important clinical consequence following envenomation by Lachesis muta muta, usually attenuated or prevented by administration of antivenom. The venom of L. m. muta contains both a metalloproteinase fibrinogenase and a serine protease thrombin-like enzyme, and exposure of fibrinogen to iron (Fe) and carbon monoxide (CO) has been demonstrated to decrease its catalysis by such enzymes. Using thrombelastographic analytical techniques, it was determined that this venom displayed weak procoagulant effects combined with fibrinogenolytic effects, and pretreatment of plasma with Fe and CO markedly attenuated venom-mediated effects. Additional experiments involving heparin exposure and varying calcium concentrations demonstrated that modification of fibrinogen with Fe and CO in human plasma rendered fibrinogen not recognizable to the fibrinogenolytic metalloproteinase but did not prevent polymerization by the thrombin-like serine protease. Lastly, when venom was exposed to CO in isolation and then placed in plasma, the fibrinogenase was inhibited but the thrombin-like enzyme was not inhibited. In sum, utilizing relatively facile modifications, we demonstrated with thrombelastography that Fe and/or CO addition can protect human plasmatic coagulation from fibrinogenase activity but not the effects of the thrombin-like activity of L. m. muta venom.

Original languageEnglish (US)
Pages (from-to)727-733
Number of pages7
JournalHuman and Experimental Toxicology
Volume36
Issue number7
DOIs
StatePublished - Jul 1 2017

Keywords

  • carbon monoxide
  • fibrinogen
  • iron
  • Lachesis muta muta
  • metalloproteinase
  • serine protease
  • thrombelastography

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Fingerprint Dive into the research topics of 'Effects of iron and carbon monoxide on Lachesis muta muta venom-mediated degradation of plasmatic coagulation'. Together they form a unique fingerprint.

Cite this