Effects of iron and carbon monoxide on Lachesis muta muta venom-mediated degradation of plasmatic coagulation
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Published on: June 29, 2015
1Department of Anesthesiology, University of Arizona College of Medicine, Tucson, AZ, USA.
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.
Insights
Iron and carbon monoxide protect human plasma from Lachesis muta muta venom
Area of Science:
- Biochemistry
- Toxicology
- Hematology
Background:
- Hypofibrinogenemia is a significant clinical issue after Lachesis muta muta envenomation.
- Lachesis muta muta venom contains fibrinogenolytic metalloproteinase and thrombin-like serine protease enzymes.
- Iron (Fe) and carbon monoxide (CO) exposure can reduce fibrinogen catalysis by these enzymes.
Purpose of the Study:
- To investigate the protective effects of Fe and CO on human plasma coagulation against Lachesis muta muta venom.
- To differentiate the impact of Fe and CO on the venom's metalloproteinase and thrombin-like enzyme activities.
Main Methods:
- Thrombelastographic analytical techniques were employed.
- Human plasma was pretreated with Fe and CO.
- Experiments involved heparin and varying calcium concentrations.
- Venom was exposed to CO in isolation before plasma addition.
Main Results:
- Fe and CO pretreatment of plasma significantly attenuated venom-induced hypofibrinogenemia and procoagulant effects.
- Fe and CO modification rendered fibrinogen unrecognizable to the metalloproteinase but not the thrombin-like enzyme.
- CO exposure inhibited the venom's fibrinogenase but not its thrombin-like enzyme activity.
Conclusions:
- Fe and/or CO addition offers protection against the fibrinogenolytic activity of Lachesis muta muta venom.
- These modifications do not inhibit the thrombin-like enzyme's procoagulant effects.
- Facile modifications with Fe and CO show potential in mitigating specific venom-induced coagulation disturbances.
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